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Archive for the ‘Bone Marrow Stem Cells’ Category

Lion-hearted fighter beats the odds – The Straits Times

Ten-year-old Boon Kye Feng prances around the living room in furry purple pants that match the lion's head he is wearing.

He lifts the head and moves it from side to side to a beat only he can hear.

Even when the little lion gets thirsty, he drinks water through the opening in the head.

Seeing him at play, it may be difficult for strangers to tell that he has spent almost half his life battling leukaemia.

His family fought it along with him, gifting two transplants - cord blood from his baby sister and stem cells from his mother - to keep him alive.


I believe Kye Feng is a 'miracle'. We have all learnt a lot from him, not only in the science of managing the disease and the doctor-patient relationship, but also in his love of life, and his fearlessness and resilience, despite the years of pain and suffering.

ASSOCIATE PROFESSOR TAN POH LIN, from the paediatric haematology- oncology division of NUH.

Despite the intensive treatment, his parents said he had remained positive and playful.

It had started in late 2011 when Kye Feng developed spots and bruises which his parents thought were sandfly bites.

When the spots appeared a second time, his mother, Mrs Celine Boon, decided to take him for a check-up.

Doctors found that his white blood cell count was very high and told the family he could have leukaemia (cancer of the blood).

It was diagnosed as juvenile myelomonocytic leukaemia (JMML), a rare form of the disease.

But Mrs Boon, 38, was not too surprised.

This was because Kye Feng and his twin brother, Kye Teck, had previously developed juvenile xanthogranuloma (JXG), a skin disorder that is usually benign and self-limiting.

They also have an older sister, now 16, who was unaffected.

While reading up on JXG earlier, Mrs Boon had come across a potential link to JMML.

She said: "Still, I had never expected that it would happen to my son. I was quite alarmed."

JMML is so rare that blood samples had to be sent to Germany to confirm the diagnosis.

Kye Feng began chemotherapy at KK Women's and Children's Hospital (KKH) in 2012 to control the condition while waiting for a bone marrow transplant.

Although KKH doctors had not seen a JMML case in about 10 years, they did the transplant as there were few other options.

His father, Mr Roy Boon, 46, said: "It was all trial and error. There's no exact treatment for JMML."

Mrs Boon was then pregnant with their fourth child and doctors said the baby girl's cord blood could be used for the transplant as there is a 25 per cent chance of a match between siblings.

Juvenile myelomonocytic leukaemia (JMML) is a very rare form of childhood leukaemia. The hallmark symptom of the disease is the increased number of white blood cells known as monocytes.

Normal monocytes protect the body from infections, but those in patients with this leukaemia are cancerous and reproduce uncontrollably. The monocytes may then infiltrate organs such as the liver, spleen, lungs, lymph nodes and even skin.

In Western countries, one in a million children are afflicted with the disease each year. Based on Singapore population statistics last year, there is an average of one case every three years.

For the majority of JMML patients, a haematopoietic - or blood forming - stem cell transplant (HSCT) is the only curative option.

Stem cells are cells that have the potential for self-renewal and differentiation. They can develop into different forms, including white blood cells, red blood cells and platelets. Such a transplant can help patients develop new and healthy blood cells.

Stem cells can be found in the bone marrow, blood, fat tissue and placenta. They are abundant in the bone marrow but, even so, make up only 1 per cent of all cells there.

They can be "harvested" directly from the bone marrow or from the blood, whether they are from an adult volunteer or from umbilical cord blood.

The bone marrow must be stimulated to coax or force the stem cells into the peripheral blood system, but techniques are well-tested and safe.

After undergoing HSCT, 50 per cent of the patients will go on to become long-term survivors.

Abigail Ng

Source: Associate Professor Tan Poh Lin, senior consultant at the division of paediatric haematology-oncology, National University Hospital.

Thankfully, it was a full match for Kye Feng, who had the transplant and recovered well.

He looked forward to starting Primary 1 with his brother.

But before the March holidays of his first year in school, doctors noticed that the percentage of donor cells in him was beginning to fall, signalling that there could be a problem.

When it became clear that the cancer had returned, Mrs Boon said she broke down and cried.

"I was shocked. There weren't any physical symptoms. Why did it happen so quickly? It wasn't even one year after the transplant and things had looked so promising," she said.


The family sought a second opinion from the National University Hospital (NUH) and entered into the care of Associate Professor Tan Poh Lin from the paediatric haematology-oncology division.

While doctors from both hospitals suggested a second transplant for Kye Feng, there was more bad news.

His illness was mutating into mixed-phenotype acute leukaemia, a combination of two forms of cancer.

He also faced a life-threatening infection that caused high fever and bloating.

Besides beginning palliative care to improve his quality of life, the family continued to push for treatment, including natural killer-cell therapy and the removal of Kye Feng's enlarged spleen in a complicated seven-hour operation.

Even though the test results showed that leukaemic cells remained in his bone marrow, Kye Feng had a second transplant in September 2015, this time using stem cells from his mother.

Doctors usually recommend transplants only when patients register no leukaemic cells.

Mrs Boon said: "If he didn't have the transplant, he would have only six months more. With the transplant, he would at least have a chance of recovery.

"He was fighting hard. If I didn't give him the chance, I would never know if he could have survived."

Kye Feng responded well to his mother's stem cells.

Dr Tan said: "I believe Kye Feng is a 'miracle'. We have all learnt a lot from him, not only in the science of managing the disease and the doctor-patient relationship, but also in his love of life, and his fearlessness and resilience, despite the years of pain and suffering."

The crucial three months after the transplant passed by without issue, but the boy developed a graft versus host disease (GVHD) one year later.

Still, his parents were relieved that it was not a second relapse.

He was put on medication for GVHD and will recover completely.

In the meantime, the family is treasuring the time they can spend together.

Mrs Boon said: "We will relax and go with the flow, as long as Kye Feng is happy."

Continued here:
Lion-hearted fighter beats the odds - The Straits Times

5 reasons you should sign up for the bone marrow registry right now – New York Daily News


Saturday, February 11, 2017, 5:00 AM

So, bless your heart, youve already signed up for your states organ donor registry. Now its time to kick your lifesaving quest up a notch and sign up for the National Marrow Donor Program, which helps match potential donors with patients fighting leukemia, lymphoma and other deadly diseases.

Here are five reasons to throw your name in the hat, if you needed some convincing:

You can join in person by stopping by a registration drive or by spending a few minutes on Either way, youll get a registration kit to provide a cheek swab, which the organization uses to identify tissue type and match with a patient.

People aged 18 to 44 hit the sweet spot, as theyre called upon 90% of the time the younger the donor, the smoother the recovery for both patient and donor, said Lauren Wollny, the New Jersey/New York community engagement representative for the nonprofit Icla Da Silva Foundation. The 45- to 60-year-old crowd can still sign up, albeit for a $100 tax-deductible fee that helps the nonprofit cover costs.

Bradley Cooper urges public to join bone marrow registry

Just 1 in 430 volunteers ever even get a call to begin the donation process.

Once youre identified as a match, youll submit to a blood test, physical exam and pregnancy test, all free of charge. A doctor will then recommend one of two procedures: a nonsurgical peripheral blood stem cell (PBSC) donation (75% of the time), or bone marrow donation (25%), which involves surgery and anesthesia but isnt nearly as horrifying as youve heard.

For PBSC, the most common method, youll receive an injection of the drug filgrastim for five days leading up to the donation. On the big day, youll head to a clinic or blood center to have a needle draw blood from one arm, pass it through a machine that isolates the blood-forming cells, and return the blood to the other arm voila. Depending on the size of both patient and donor, it can take four to eight hours which you might use to reflect on what a terrific thing youre doing for a total stranger.

For bone marrow donation youll head to the OR, where a doctor will siphon liquid marrow from the back of your pelvic bone with a needle. The anesthesia will keep you numb, and though you may later feel back or hip soreness, fatigue and other side effects, you should be back to your normal routine within a week.

EXCLUSIVE: Bone marrow recipients to meet FDNY donors

33 photos view gallery

This is the one that gets a really bad rap, Wollny told the Daily News. Its not as bad as people make it out to be.

All in all, the average length of the donation process from start to finish is about 20 to 30 hours over a month or two and your own personal case manager will see you through the entire thing.

People are most likely to match with someone of the same ethnic background since the tissue types used for matching are inherited and the registry is starved for donors who are black or African American, Hispanic, Hawaiian/Pacific Islander, Asian, Alaska native, Native American and multiracial. If one of those describes your ancestry, go be a hero, please.

The Fort Lee, N.J., 12-year-old was diagnosed with acute myeloid leukemia last year, undergoing several rounds of chemo and a bone marrow transplant from her mom before eventually being pronounced cancer-free. But after a relapse in November, Lopez is fighting for her life once again and desperately in need of another bone marrow transplant.

New York tries to increase organ donations to those in need

The Long Island City-based Icla Da Silva Foundation will hold combo registry drive/fundraisers for the tween in New Jersey (Fort Lee and Union City), Georgia, Texas and Florida this Sunday. If youre free and in good health, you should go.

We hope to find Briana a match, and if we find other people a match as well, fantastic, Wollny said. Its so simple to save a life if it was you, wouldnt you want someone to do that for you?

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5 reasons you should sign up for the bone marrow registry right now - New York Daily News

Stem cell registry drive at SAU Feb. 14-15 – SAU

When three Southern Arkansas University nursing students started organizing next weeks stem cell registry drive more than three months ago, they were not aware that a member of the Mulerider family is one of more than 1,400 whose life could be saved.

The stem cell/bone marrow registry drive is scheduled for 9 a.m.-3:30 p.m. on February 14-15 both in the Reynolds Center Rotunda and the SAU Baptist Collegiate Ministry. For more information, contact Dr. Becky Parnell at (870)235-4365 or at

The SAU BSN students initially behind the project are Renee Langley, Tabitha Elliott and Courtney Owens. Parnell explained that while attending the Arkansas Student Nurses Association annual meeting in Little Rock, the students were introduced to the need for bone marrow donors. They even registered to be possible donors themselves. She said they realized this project was a perfect example of how nurses can impact the care of people outside the normal hospitalized patient.

They recognized how many people this could potentially impact and wanted to recruit more people (to register), said Parnell. I have seen the bone marrow process it is truly a life-saving intervention for many people that are devastated by leukemia.

When Parnell began promoting the registry event on campus, it was brought to her attention that the daughter of Magnolia native, 1984 SAU alum and Board of Governors Chair Beth Galway, Sydney, is suffering with acute myeloid leukemia and in dire need of a bone marrow transplant.

When Sydney was diagnosed with acute myeloid leukemia, the doctors told us that Sydneys only cure would come from a bone marrow transplant. The doctors were, and are, confident of the success of her treatment due to the fact that she has a high chance to find a perfect bone marrow donor, said Galway.

Her increased chance of finding a match, Galway explained, is simply because she is a Caucasian female which has one of the highest bone marrow donor rates. She has a 97% chance to find a donor.

Of course, the first donor they looked at was her sister. A sibling has only a 25% chance to be a match; a parent even less. Sydneys sister was not a match, said Galway.

Donor matches are generally based on race. With todays diverse community, the need for bone marrow donors from minority and mixed race groups is high. An African American patient has only a 66% chance to find a match.

The doctors and nurses that I have talked to indicate that the need is huge for African Americans as well as donors from India, said Galway.

She said that the treatment for Sydney, who is a sophomore in college, is now in phase 3. Her next step is a bone marrow transplant.

We hope to have a perfect match for her and pray that the donor will be willing to do all that is necessary for providing the blood or bone marrow needed for the transplant, said Galway.

The drive is being sponsored by SAUs Department of Nursing and University Health Services. Junior and senior BSN students will also be assisting in the bone marrow drive as a professional development activity.

Becoming a member of a stem cell/bone marrow registry only requires that you provide a swab of the cells inside your cheek. To register is a painless and fast way to possibly save a life.

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Stem cell registry drive at SAU Feb. 14-15 - SAU

OCASCR scientists make progress in TSET-funded adult stem cell research –

OCASCR scientist Lin Liu at work. Photo provided.

Working together, scientists from Oklahoma State University, the University of Oklahoma Health Sciences Center and the Oklahoma Medical Research Foundation are advancing adult stem cell research to treat some of todays most devastating diseases.

Under the umbrella of the Oklahoma Center for Adult Stem Cell Research (OCASCR), created with funding from the Oklahoma Tobacco Settlement Endowment Trust, these scientists have amassed groundbreaking findings in one of the fastest growing areas of medical research.

We have made exciting progress, said OCASCR scientist Lin Liu, director of the Oklahoma Center for Respiratory and Infectious Diseases and director of the Interdisciplinary Program in Regenerative Medicine at Oklahoma State University.

We can convert adult stem cells into lung cells using our engineering process in petri dishes, which offers the possibility to repair damaged lung tissues in lung diseases, said Liu, whose research primarily focuses on lung and respiratory biology and diseases.

Using our engineered cells, we can also reverse some pathological features. These studies give us hope for an eventual application of these cells in humans.

Adult stem cells in the body are capable of renewing themselves and becoming various types of cells.

Until recently, stem cell treatments were largely restricted to blood diseases. However, new studies suggest many other types of adult stem cells can be used for medical treatment, and the Oklahoma Center for Adult Stem Cell Research was created to promote this branch of research.

OCASCR scientist Lin Liu and his team discussing their work. Photo provided.

Liu said the discipline provides hope for many ailments.

What most fascinated me in stem cell research is the hope that we may be able to use stem cells from our own body; for example, bone marrow or fat tissues to cure lung diseases, Liu said.

It is impossible to know exactly which diseases will respond to treatments.However, results of early experiments suggest many diseases should benefit from this type of research, including lung, heart, Alzheimers and Parkinsons diseases, as well as cancer, diabetes and spinal cord injuries. The field is often referred to as regenerative medicine, because of the potential to create good cells in place of bad ones.

While the application of stem cells can be broad, Liu hopes that his TSET-funded work will help develop treatments for diseases caused by tobacco use.

The goal of my research team is to find cures for lung diseases, Liu said. One such disease is chronic obstructive pulmonary disease (COPD).

COPD is the third leading cause of death in the country and cigarette smoking is the leading cause of COPD.

Cigarette smoking is also a risk factor for another fatal lung disease, idiopathic pulmonary fibrosis (IPF), which has a mean life expectancy of 3 to 5 years after diagnosis, he added.

There is no cure for COPD or IPF. The current treatments of COPD and IPF only reduce symptoms or slow the disease progression.

Using OCASCR/TSET funding, my team is researching the possibility to engineer adult stem cells using small RNA molecules existing in the body to cure COPD, IPF and other lung diseases such as pneumonia caused by flu, Liu said.

This is vital research, considering that more than11 million peoplehave been diagnosed with COPD, but millions more may have the disease without even knowing it, according to the American Lung Association.

Despite declining smoking rates and increased smokefree environments, tobacco use continues to cause widespread health challenges and scientists will continue working to develop treatments to deal with the consequences of smoking.

We need to educate the public more regarding the harms of cigarette smoking, Liu said. My research may offer future medicines for lung diseases caused by cigarette smoking.

Under the umbrella of the Oklahoma Center for Adult Stem Cell Research (OCASCR), created with funding from the Oklahoma Tobacco Settlement Endowment Trust, these scientists have amassed groundbreaking findings in one of the fastest growing areas of medical research. Photo provided.

Liu has been conducting research in the field of lung biology and diseases for more than two decades.

However, his interests in adult stem cell therapy began in 2010 when OCASCR was established through a grant with TSET, which provided funding to Oklahoma researchers for stem cell research.

I probably would have never gotten my feet into stem cell research without OCASCR funding support, he said. OCASCR funding also facilitated the establishment of the Interdisciplinary Program in Regenerative Medicine at OSU.

These days, Liu finds himself fully immersed in the exciting world of adult stem cell research and collaborating with some of Oklahomas best scientific minds.

Dr. Liu and his colleagues are really thriving. It was clear seven years ago that regenerative medicine was a hot topic and we already had excellent scientists in the Oklahoma, said Dr. Paul Kincade, founding scientific director of OCASCR. All they needed was some resources to re-direct and support their efforts. OSU investigators are using instruments and research grants supplied by OCASCR to compete with groups worldwide. TSET can point to their achievements with pride.

The Oklahoma Center for Adult Stem Cell Research represents collaboration between scientists all across the state, aiming to promote studies by Oklahoma scientists who are working with stem cells present in adult tissues.

The center opened in 2010 and has enhanced adult stem cell research by providing grant funding for researchers, encouraging recruitment of scientists and providing education to the people of Oklahoma.

We are fortunate that the collaboration at the Oklahoma Center for Adult Stem Cell Research is yielding such positive results, said John Woods, TSET executive director. This research is leading to ground breaking discoveries and attracting new researchers to the field. TSET is proud to fund that investments for Oklahomans.

Funding research is a major focus for TSET and it comes with benefits reaching beyond the lab. For every $1 TSET has invested at OCASCR, scientists have been able to attract an additional $4 for research at Oklahoma institutions, TSET officials said.

TSET also supports medical research conducted by the Stephenson Cancer Center and the Oklahoma Tobacco Research Center.

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OCASCR scientists make progress in TSET-funded adult stem cell research -

Genetic profiling can guide stem cell transplantation for patients with … – Science Daily

Genetic profiling can guide stem cell transplantation for patients with ...
Science Daily
A single blood test and basic information about a patient's medical status can indicate which patients with myelodysplastic syndrome (MDS) are likely to benefit ...

and more »

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Genetic profiling can guide stem cell transplantation for patients with ... - Science Daily

Can storing your stem cells be the key to fighting disease and living longer? – WXYZ

(WXYZ) - When we get sick, it's common for us to reach for some medicine or maybe even have surgery to deal with disease or pain, but what if you could use your own healthy cells to fight back instead?

Right now, there's a procedure being performed in metro Detroit where healthy stem cells are stored so they can be reintroduced to your system and potentially have life changing or life saving benefits.

Dr. Michael Schenden is the first plastic surgeon in the US to perform the Forever Labs stem cell collection. He starts by harvesting her bone marrow to save those healthy stem cells.

"They should be available for many, many different medical applications is a wonderful thing," says Dr. Schenden.

The company behind this procedure is based in Ann Arbor and it's called Forever Labs.

We're told about 30 people have decided to store their stem cells this way. Sonja Michelsen is one of them. She had her daughter in her early 40s and felt like storing her own stem cells could pay off in the future.

"I want to be able to be here with her throughout her life," she says.

She knows there's no guarantee banking her stem cells will help her in the future, but she sees it as an investment that could pay off if her health takes a turn.

"To have that peace of mind that you do have something to use down the road .. is huge," she says.

Steven Clausnitzer is CEO of Forever Labs. He says by re-introducing your own healthy cells, you may be able to fight disease in the future.

"There are a number of ways people are already using these cells. Maybe the most promising .. orthopedic surgeons .. are reintroducing them into joints in lieu of surgery," he says.

Clausnitzer says there are about 500 clinical trials right now that are using stem cells that, one day, may be able to treat everything from osteoarthritis to multiple scleroses to cardiovascular disease.

This kind of stem cell banking is a 15 minute outpatient procedure. It starts with a local anesthetic in the lower back.

He says the number of your stem cells diminishes with age, as does their therapeutic quality.

"My stem cells were stored at 38. I'm going to turn 40 this year. I rest assured knowing I have my 38-year-old stem cells rendered biologically inert. They're no longer aging .. even as I do," says Clausnitzer.

Mark Katakowski is president of Forever Labs. He says his research showed him the rejuvenating and healing power of stem cells in animals. He believes it can have the same effect in humans.

He says the best time to store the stem cells is when you're young.

"There's a slower decline between 20 and 40 years-old and then it picks up. When you put them in the right place at the right time, they can actually improve recovery in a bunch of therapeutic applications," he says.

Katakowski says there's no limit as to how long they can be stored.

Should a person pass away, their stored stem cells would be destroyed unless arrangements have been made for them to be given to a family member.

At this point, the procedure is not FDA approved. The Forever Labs stem cell collection isn't covered by insurance. It costs around $3,500 to have the procedure done and $250 a year for storage.

The company says it plans to bring the first clinical trials for longevity to market in the next 7-10 years, once there is a large enough differential time between when our first clients stored their cells and can then reintroduce.

It says its goal is that its clientele will be able to participate in the first longevity based human trials utilizing autologous stem cell treatments of healthy individuals.

To learn more about Forever Labs, go to:

Can storing your stem cells be the key to fighting disease and living longer? - WXYZ

Bone marrow registration drive planned to honor Salina man – Salina Journal (subscription)

A 45-year-old Salina man who was diagnosed with leukemia in November is being honored by a bone marrow registration drive Saturday being held at his church.

This is open to the whole community we want to stress that, said Linda Ourada, a member of the health ministry committee at St. Mary Queen of the Universe Catholic Church Parish Center, 230 E. Cloud. The drive will be held from 10 a.m. to 2 p.m. Saturday at the parish center.

Its possible that Phong Vos sister is a match for him, said Vos wife, Mary Pham.

More blood work is planned to determine if the match is close enough. In the meanwhile, the effort to sign up possible donors for Vo or anyone else who needs a bone marrow or peripheral blood stem cell donation is planned.

Pam Welsh, of Salina, said that more than a decade ago, she had her cheek swabbed during a bone marrow registration drive when a Bennington woman needed a match. She said she was called about a year later and told she was one of three people who were a possible match for a patient. She said she went to Salina Regional Health Center to have blood drawn for further testing.

I was given a choice if I wanted to continue in the process, she said. There was never any pressure.

She said that after the blood tests showed she was a good match for the patient, a nurse came to her house to give her shots to boost her stem cell count. Then she and a friend drove to a Wichita hospital, where she underwent an outpatient procedure during which her blood was drawn from one arm and passed through a machine that filtered out blood stem cells before the blood was returned to her other arm. Welsh said the procedure took one day, and then she took the next day off to recover. All expenses were paid by DKMS, an international organization that fights blood cancer and blood disorders, she said.

She said she found out that her blood was given to a 55-year-old man with some form of leukemia. She was told he was still alive when DKMS contacted her for a five-year checkup.

Although she never met him, Welsh said that for her there was a huge reward in knowing that I was able to help this man knowing that I gave him more years.

Its just a good feeling, she said.

Pham said Vo started feeling ill in October and has since undergone chemotherapy at Via Christi Hospital in Wichita and the University of Kansas Medical Center in Kansas City. However, the leukemia has persisted.

Pham, who works for Schwans, has lived in Salina since her grandparents and an aunt, who had lived here since 1975, acted as her sponsors when she immigrated from Vietnam about 21 years ago. She met Vo, who moved here in the late 1990s, at work, and they were married at St. Marys. They have four sons, ages 11, 11, 10 and 8, who have missed their father during his long hospital stays.

When my husband got sick, I was panicked, and I was like, What do I need to do? I dont know what to do, Pham said. Soon she was told about DKMS, which will attempt to match potential donors who register at the Salina drive with Vo and other patients.

The bone marrow registration process for DKMS is simple, said Linda Ourada, who is helping to organize the event.

Its not like drawing blood, Ourada said. People get this mixed up with a blood drive. Theres no blood involved.

A swab is taken from the inside of the cheek, which is then sent for DNA analysis and entered into a global donor computer registry that already includes information about 7 million potential donors.

Every day in the United States, there are 14,000 people waiting for this blood stem cell donation, and only 30 percent get a family match, so that leaves 70 percent out there looking for a suitable donation from someone like us, Ourada said.

Ourada said that in 2012, more than 250 people registered and nine potential matches were contacted for further testing during a bone marrow drive at the church to honor a St. Louis family with Salina ties who had four boys with a rare form of blood cancer.

There is no cost to register as a donor, although monetary donations are being accepted to cover the approximately $65 in costs associated with registering each possible donor.

Potential donors must be between the ages of 18 and 55, in general good health and be willing to donate should their marrow be matched with a person who needs it. Further details about weight and height requirements or other limiting factors can be found at

The donation process may be accomplished one of two ways, depending on the patients needs. The preferred method is a blood transfusion, but for some patients, an actual bone marrow graft is necessary. The marrow is harvested through a hollow needle from a hip bone in an outpatient surgical procedure.

Bone marrow could be used to treat blood cancers, anemias, genetic disorders and other life-threatening ailments.

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Bone marrow registration drive planned to honor Salina man - Salina Journal (subscription)

More people to get access to life-saving stem cell transplants – Erie Media

This post was originally published on this site New Facility at Sunnybrook Part of Plan to Expand Care for People with Blood Diseases

Ontario is investing in a new facility at Sunnybrook Health Sciences Centre that will offer specialized treatment for people with blood cancers such as leukemia.

Premier Kathleen Wynne was at Sunnybrook in Toronto Tuesday to announce the governments support for a new Complex Malignant Haematology (CMH) site. Sunnybrook will become the second hospital in the Greater Toronto Area along with Princess Margaret Cancer Care to provide a full range of potentially life-saving CMH services, including stem cell transplants.

Ontario is also improving treatment for people with blood diseases by:

Investing to improve care for people with blood cancers and disorders is part of our plan to build a better Ontario by providing patients with faster access to the right health care.

Kathleen Wynne: Premier of Ontario

Stem cell transplants can help lessen the terrible toll that cancer takes on families. We are providing support so hospitals can offer more patients access to a life-saving treatment and the chance for a new lease on life.

Dr. Eric Hoskins: Minister of Health and Long-Term Care

Today marks a major milestone for Ontario patients needing stem cell transplants. With this investment, patients will have better access to timely service and state-of-the-art treatment, but most importantly, more patients will be able to receive stem cell transplants right here in Ontario.

Dr. Barry McLellan: President and CEO, Sunnybrook Health Sciences Centre

This is a life-saving investment. We are grateful to the Ontario government for the funding to provide care and build a new state-of-the-art facility for patients who are afflicted with this serious illness.

Michael Sherar: President and CEO, Cancer Care Ontario; Co-convener, Complex Malignant Hematology Hematopoietic Cell Therapy Consultation Group

Sunnybrook Health Sciences Centre is an important and valued partner in Ontarios cancer care system. The addition of a new Complex Malignant Haematology site is a critical step in our efforts to ensure that patients receive timely access to transplant services in Ontario.

Source Government of Ontario press release

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More people to get access to life-saving stem cell transplants - Erie Media

‘Magic’ blood test could make bone marrow transplants for blood … – Cancer Research UK

A blood test could help predict the risk of complication following a bone marrow transplant in some blood cancer patients, according to a new US study.

The test could help identify which patients given a transplant are likely to develop a potentially fatal complication, the researchers report in The Journal of Clinical Investigation Insight.

"The test worked in different hospitals and in different groups of patients in the US and Europe, suggesting that it could be used widely" Professor Ronjon Chakraverty, Cancer Research UK

In doing so, the test could allow early intervention and potentially save many lives, said lead researcher Professor James Ferrara from Mount Sinai School of Medicine.

Bone marrow transplants, in which a patients blood stem cells are replaced with those from a donor, are given to some patients with blood cancer to cure their disease. But around half of patients who receive the procedure develop a serious and often fatal complication called graft-versus-host disease (GVHD).

This happens when the donated immune cells recognise the patients body as a threat and launch an attack against it, causing inflammation that sometimes doesnt respond to treatment.

For this latest study, researchers from 11 cancer centres in the US and Europe looked at blood samples from almost 1,300 bone marrow transplant patients to see if they could predict whether a patient will develop GVHD, and also their outlook.

They developed a test, called MAGIC (Mount Sinai Acute GVHD International Consortium), looked at four different molecules in the blood. The researchers found that measuring the levels of two of these molecules ST2 and REG3a just one week after the transplant procedure, could help identify those at high risk of developing the complication and dying.

Researchers at Mount Sinai are now using these results to design clinical trials looking into whether certain immunotherapy drugs, normally given at the onset of GVHD, could improve the outlook for some patients if given earlier on, after the test identifies them as high risk.

Professor Ronjon Chakraverty, a Cancer Research UK expert on stem cell transplants, said: This study reveals that a blood test performed just one week following a bone marrow transplant accurately identifies which patients are at the greatest risk of this life-threatening condition.

Importantly, the test worked in different hospitals and in different groups of patients in the US and Europe, suggesting that it could be used widely. Tests such as this could spot patients who are most at risk, and make sure they get special targeted treatment before GVHD develops.

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'Magic' blood test could make bone marrow transplants for blood ... - Cancer Research UK

Jillian Altenburg: Sharing her gift of lifeand bone marrowwith young leukemia patient – Cut Bank Pioneer Press

An act of kindness can change your life in a positive way. But how much better would it be if that same act ends up changing someone elses life in an amazing way too? Jillian Altenburg can answer that.

It will change me for the better, but I am even happier I have the ability to change someone elses life for the better, Jillian said.

This month, Jillian will go through a bone marrow donor procedure for a little child struggling with leukemia. Not only will this change Jillian forever, but it gives a small child a new chance at life.

Jillian, the daughter of Gary Altenburg and Lori Altenburg, is a Cut Bank High School 2013 graduate. She will be part of another graduation this May when she receives her nursing degree from the MSU-BSN college of nursing program in Great Falls.

Jillian first learned about being a bone marrow donor while in her freshman year of college at MSU-Bozeman. It was during one of my classes we heard about a child who was looking for a bone marrow match and after class the organization called Be the Match was introduced to us.

Be the Match is an organization that matches bone marrow donors to patients in need of a bone marrow transplant. Jillian became a potential donor that day after class when she had her cheek swabbed and entered into the program.

It was a few years before she heard anything from Be the Match, but this past December Jillian received a call saying she could be a match for a patient needing bone marrow.

I didnt know if I was the only match or if there were other potential matches too, Jillian stated. They asked me to do some blood work and they said it usually takes 60 days to determine if I would be a perfect match. But it only took a week for them to get back to me and let me know I was a perfect match for this little child with leukemia.

It was then that things started happening fast for Jillian. They told me that the child was in remission and that there is a window of time to do the procedure, so they gave me the date it would be done and where I needed to be for the procedure and explained what would be happening. And Be the Match would be picking up the tab for everything.

According to Jillian, there are two ways to collect bone marrow. One of those is by putting needles in my arm to gather stem cells. The other is by cutting a slit on both sides of my pelvis and inserting a hollow needle into the bone to pull out what they need. Normally they can take up to six cups of bone marrow, but with this being a child needing the bone marrow, they probably will not need that much.

After the procedure, Jillian will be discharged but will need to stay close to the hospital for another night in a hotel to make sure all is okay. Once that is determined, she can return home.

They say the procedure is painful and I will be sore. But ever since I learned I was a match, there was no choice in this for me. I actually feel like the lucky one, having this opportunity to help this child, Jillian said.

Within seven days of harvesting Jillians bone marrow, the child will receive the bone marrow that is so desperately needed for survival. During that time, Jillian should feel better and better each day. And within two weeks of having made the donation, Jillians body will have replaced the bone marrow taken from her.

Even though Be the Match tells all their potential donors that they can opt out of the program at any time, that was not an option for Jillian. Once they start prepping the patient to receive a bone marrow transplant, they really dont want people to say they have changed their minds. I have no intention of doing that anyway. When they called me, it was not a decision I had to think about. I knew I was going to do it. It feels good to be able to help someone and change their life for the better, she said.

The day Jillian shared the news with her mom Lori, that she was a potential bone marrow match for someone, Lori said, I got that warm, fuzzy feeling, but as we spoke longer it turned to worry, mostly for this child who has had to deal with these awful circumstances. I knew Jillian would be fine. She is strong, very physically fit and young. She has everything going for her in being a good donor.

Lori will be accompanying Jillian when she has the procedure done and will be there for her all the way through to recovery. We have always teased Jillian that she is still attached to her moms umbilical cord, so we both know I have to go, even though I know it doesnt stretch quite that far, laughed Lori.

Lori admitted she did not know Jillian had even put her name into the Be the Match program. We have lost many loved ones due to cancer, with number one being Jillians Grama Nancy (Loris mom). Even so, when I got the call from Jillian that she was contacted by the Be the Match program because she was a possible bone marrow match, it was very, very surprising. But I feel super proud and very blessed that she was chosen. To say I am not a little nervous would be a fib, but she will be in good hands and we know friends and family are praying for her and the child who will receive the donation, Lori shared.

For a year following the transplant, Jillian will not know the name of the child she made the donation to. I can find out through Be the Match how this little one is doing, but for up to a year they want me to remain anonymous. After a year, we can have contact.

As Jillian said, she knew without a doubt, she would be going through this procedure the minute she was called and told she was a perfect match. And while she admitted she is a little scared, she countered that with, It will be worth it.

There are two lives being changed with one procedure. Jillians life will be forever changed by this. And the young child? With Jillians donation, there is hope that many years can be added to that young little life.

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Jillian Altenburg: Sharing her gift of lifeand bone marrowwith young leukemia patient - Cut Bank Pioneer Press

USM women’s soccer players organize bone marrow drive for teammate with rare disease – Press Herald

Ally Little described the past month of her life as a nightmare from which she just cant wake up.

On Dec. 22, the University of Southern Maine soccer player learned she had a rare and life-threatening disease in which her bone marrow stops producing healthy blood cells. However, the words severe aplastic anemia meant nothing to Little at the time.

Its really hard because I didnt know what this was before I had it, said Little, a 20-year-old sophomore from Stoneham, Massachusetts. No one has really heard of aplastic anemia or what the treatment is.

A bone marrow transplant is the cure for this disease, and Little has yet to find a matching donor. Littles teammates have organized a bone marrow donor registry drive from 9 a.m. to 1 p.m. Wednesday at Abromson Mezzanine at the USM Portland campus and from 2:30 to 5:30 p.m. at Costello Complex at the Gorham campus.

Diagnosed during winter break, Little broke the news to her teammates on social media.

It hit home, said USM womens soccer coach Lisa Petruccelli. This is really the first time someone their age at this juncture is struggling with something like this.

Littles initial symptoms didnt seem serious. She started getting pounding headaches around Thanksgiving, but she had gotten headaches before. Physical activities such as skiing or working out for soccer became unusually exhausting, which Little attributed to dehydration. She didnt go to her doctor until she noticed blood in her stool.

(Aplastic anemia) is believed to be an autoimmune system gone wrong, said Paul Scribner, Senior Director of Patient Advocacy Programs with the Aplastic Anemia and MDS International Foundation (AAMDS). The disease usually results from the destruction of bone marrow stem cells by the immune system. Other symptoms include infections and the tendency to bruise and bleed easily. With such innocuous warning signs, Scribner said a lot of people find out when they go to their doctor because theyre feeling run down.

After bloodwork, Little was told that her results were very abnormal. She spent the next few days in the hospital undergoing tests while doctors prepared her for the worst case scenario leukemia.

That was obviously horrifying, Little said. We didnt find out until about three days later that it was severe aplastic anemia.

Aplastic anemia is rare and can occur at any age. In the United States, about 600 to 900 people are diagnosed each year, according to AAMDS. The disease is considered severe when all three types of blood cells red blood cells (carry oxygen), white blood cells (fight infections) and platelets (help blood to clot) are very low in number.

I was kind of relieved it wasnt cancer, Little said. Then, doctors explained to me that its really not that good. It was devastating.

Little couldnt go back to school. With her compromised immune system, crowds are off limits. She cant play contact sports or do anything that could put her at risk of internal bleeding. She gets blood transfusions every week, and she can tell when shes due for another by the dizziness and headaches she gets. The long-term risk of too many transfusions, Scribner said, is iron overload.

Most days, I feel OK, Little said. I dont really feel sick, which is good. But its hard to remember I cant do certain things.

Little is buying time until she can get a bone marrow transplant. Bone marrow is the spongy tissue inside of the bones that produces the bodys blood cells. She didnt find a match among her family or with Be The Match a national bone marrow registry that contains 22.5 million adult donors.

Registering at the drive is simple. Potential donors must be between 18-44 years old and fill out basic paperwork and get their cheek swabbed to have their tissue type added to the registry a process that takes just a few minutes. After that, they will remain registered until age 61, unless they withdraw.

However for those in need of bone marrow finding a perfect match is not so easy.

Think about Megabucks and how hard it is to match that, said Jackie McLoon, Assistant Account Executive with Rhode Island Blood Center as well as a bone marrow donor. McLoon, a representative with Be the Match, has helped the USM soccer team organize its drive. Everyday, there are donors getting added to the database. Hopefully, her match shows up one of these days.

Only 30 percent of patients in need of a marrow transplant have a matching donor in their family. Be The Match helps the 14,000 patients a year who suffer from leukemia, lymphoma or a variety of bone marrow functioning diseases. McLoon said a protein called human leukocyte antigen (HLA) is used to match patients with donors, and potential matches will then undergo bloodwork to determine if they would be a good fit. Only about 1 in 500 registrants go on to actually donate marrow.

There are 10 things that they are supposed to match, Little said. They think one of my 10 is very rare.

But her teammates are optimistic. On Saturday, they attended a home basketball game clad in T-shirts adorned with the phrase: All for Ally. They gushed about Littles kind personality and reminisced about all the times they crashed in her room.

Shes the best teammate ever. Shes so sweet oh my god, I love her, said Jessica Preble, a sophomore on the team. If you ask anything of her, shell drop everything and do it.

This team is kind of used to bad things happening to our girls, said Dayna Staffiere, noting that one of their teammates lost her dad at sea last season when the cargo ship El Faro sank after encountering Hurricane Joaquin. It just brings us all closer.

When Little isnt at the hospital, shes usually working on her online classes or walking her dog. She said the support from family, friends and her soccer team is what keeps her going.

Were the ones who are supposed to be strong for her, but shes so strong for us, Preble said. Just a cheek swab and some paperwork could help save her life.

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USM women's soccer players organize bone marrow drive for teammate with rare disease - Press Herald

Program seeks to boost bone marrow, stem cell donations from indigenous people – CTV News

By filling out a form, and swabbing his mouth, Harlee O'Watch could save a life.

"To find a match, because the list of donors is so low, is really unlikely," said the 22-year-old.

O'Watch is one of four young adults from Carry the Kettle First Nation who registered with the OneMatch program, which connects donors with people in need of bone marrow or stem cell transplants.

A problem for the 14 indigenous people currently waiting for a match is that, out of the 17,000 people on the Canadian registry, fewer than one per cent are indigenous.

"It doesn't give me much hope if I ever get sick and need a blood transfusion or bone marrow transplant, said OWatch.

It doesn't give me much hope because, if there's no potential matches, I'm going to die, bottom line, and I don't want to die."

Robyn Henwood works for Canadian Blood Services, which runs OneMatch. She covers Alberta to Northern Ontario and the Northwest Territories, including the Prairies, and visited Carry the Kettle to recruit. A match requires a genetic twin and indigenous people are only in Canada.

"It does get more complicated [with] these different ethnic backgrounds. . . even within First Nations that get brought into it, said Henwood.

The chances of finding a match becomes that much more difficult."

This means someone who is Cree cannot donate to someone who is Mohawk, she said.

In the past year, Canadian Blood Services has visited less than 12 reserves to help find matches for indigenous people. Carry the Kettle is Henwoods third community.

"We have been leaving messages and voicemails, not getting a lot of response back, she said.

I'm hoping a new technique will work. Things like this, this is so important to spread our message."

According to Indigenous and Northern Affairs Canada, more than 50 per cent of indigenous people live in urban centres. And yet, Henwood says finding indigenous donors in cities is also a struggle.

"Trying to get someone to sign up and commit for the next 30 to 40 years, to potentially save a stranger's life is not an easy thing to do," she said.

Henwood says informing indigenous people about one match will empower more to donate. Until then, the chance of survival for those waiting on the registry is low.

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Program seeks to boost bone marrow, stem cell donations from indigenous people - CTV News

Quebec family hopes to raise awareness for patients in need with stem cell registry drive –

Its been a long and difficult road for West Island resident Kevin Butterfill and his Fiance Natasha Camacho-Gomes.

Kevin had testicular cancer in Oct. 2015, he did chemo, he then had the tumor removed and he was in remission, Gomes said.

Its what happened in July 2016 that is causing a lot of grief for Butterfills loved ones.

He proposed to Camacho-Gomes, his girlfriend since 2009, but a week later more health complications arose.

He was diagnosed with myelodysplastic syndrome (MDS) which is a bone marrow disorder.

And to make matters even worse, Butterfill found out the MDS transformed into acute myeloid leukemia in January.

The past two years have been a roller coaster ride for Kevins mother, Heather Butterfill.

Were staying strong, Heather Butterfill said. Im very faithful that hes going to come out of this stronger than ever.

On Saturday, family and friendsgathered at a Provigo grocery store in Kirkland, encouraging those who know Kevin to sign-up to the bone marrow registry.

READ MORE:Venclexta gets accelerated approval to treat leukemia

Butterfill will need a bone marrow stem cell transplant to recover from the leukemia.

However, according to Hema-Qubec stem cell registry manager Susie Joron, the odds of the perfect match being a friend are slim.

Theres 60,000 transplants every year worldwide, Joron said. The chances of having a friend or a neighbour being matched to that one person that we know is very unlikely.

Gomes said the aim of the event is raise awareness about the stem cell donor registry.

A lot of people were interested in joining and trying to see if they were Kevins match, Camacho-Gomes said.

But a really important thing [to note] is that when you join the stem cell registry youre tested against everyone, so you have the potential to save anyones life.

Regardless of who ends up being Butterfills perfect match, friends like Jonathan Coleman are still hoping they can help.

To hear something like this happen to somebody like that, a good-hearted kid, it sucks and sad to hear, Coleman said. You want do anything you can to help him out.

READ MORE:Id do it again in a heartbeat: debunking myths around stem cell donation as #MenGiveLife kicks off

While Butterfill awaits news of a bone marrow donor for his stem cell transplant, Gomes will hope for a perfect match and move on to planning their wedding.

They set a tentative date for Victoria Day 2018.

For more information on stem cell donation and the registry, visit the Hma-Quebec website.

2017Global News, a division of Corus Entertainment Inc.

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Quebec family hopes to raise awareness for patients in need with stem cell registry drive -

Search goes on for bone marrow match for little Longworth lad … – Oxford Mail

ANDREW and Judy Kim are still searching the globe for a donor for their two-year-old son after he was diagnosed with a rare genetic condition.

The couple's son Alastair was diagnosed with chronic granulomatous disorder (CGD) in February last year.

Mr and Mrs Kim launched an appeal for help in September but the search is still on for a matching donor and their son still needs hospital treatment.

The life-threatening condition wipes out his immune system, meaning even the most minor infections leave him seriously ill.

A course of genetic therapy treatment to help him fight infections has been launched and Alastair has been treated at Oxford Children's Hospital and Great Ormond Street Hospital in London.

The only hope of a permanent cure lies in a bone marrow stem cell donor but it needs to be a 90 per cent genetic match and the family is calling for more East Asians to sign up as donors.

Mr Kim, 37, a medical research engineer, said: "It is not easy to find a match and we pray every day that it will work out.

"We have to make sure that Alastair does not get a cut because it could get infected and he does not have the ability to fight off bacteria.

"That could cascade down the line to something very dangerous for him.

"If we get ill then we have to stay away from him he loves our dog Choco Pie but he is not allowed to stroke her.

"We are doing our best to stay positive and raise awareness about his condition."

Mr and Mrs Kim, who live near Longworth with their other son Micah, five, have already searched the international register of more than four million donors but without success.

They are both of Korean descent so a matching donor will most likely be of Korean, Japanese or Chinese heritage.

The number of East Asians on international donor registers is very limited of the 617,000 registered donors in the UK just 0.5 per cent are east Asian.

The couple, who moved to Oxfordshire from Chicago nine years ago, are now appealing for people around the world, particularly East Asians, to order a free kit through a website they have set up, and take a two-minute home test to see if they could help.

Alastair has had numerous infections since he was born in September 2014.

He spent the first year-and-a-half of his life in and out of hospital but CGD is so rare, doctors never thought to test him for it but eventually a doctor at the John Radcliffe Hospital in Oxford decided to test Alastair for the condition.

The couple desperately want to find a matching donor, but also want to increase the number of East Asians on the donor register.

The couple have run several blood drives at Mrs Kim's office at Oxford University and at Harwell Oxford.

More than 90 people came forward and of those, five were able to donate blood that helped Alastair to fight infections.

Mr Kim added: "At a couple of blood drives we have found matches for other people and hopefully one day a match will found for Alastair."

To join the register go to

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Search goes on for bone marrow match for little Longworth lad ... - Oxford Mail

Yes there’s hope, but treating spinal injuries with stem cells is not a reality yet – The Conversation AU

The 2017 Australian of the Year award went to Professor Alan Mackay-Sim for his significant career in stem cell science.

The prize was linked to barbeque-stopping headlines equating his achievements to the scientific equivalent of the moon landing and paving the road to recovery for people with spinal cord injuries.

Such claims in the media imply that there is now a scientifically proven stem cell treatment for spinal cord injury. This is not the case.

For now, any clinic or headline claiming miracle cures should be viewed with caution, as they are likely to be trading on peoples hope.

Put simply, injury to the spinal cord causes damage to the nerve cells that transmit information between the brain and the rest of the body.

Depending on which part of the spine is involved, the injury can affect the nerves that control the muscles in our legs and arms; those that control bowel and bladder function and how we regulate body temperature and blood pressure; and those that carry the sensation of being touched. This occurs in part because injury and subsequent scarring affect not just the nerves but also the insulation that surrounds and protects them. The insulation the myelin sheath is damaged and the body cannot usually completely replace or regenerate this covering.

Stem cells can self-reproduce and grow into hundreds of different cell types, including nerves and the cells that make myelin. So the blue-sky vision is that stem cells could restore some nerve function by replacing missing or faulty cells, or prevent further damage caused by scarring.

Studies in animals have applied stem cells derived from sources including brain tissue, the lining of the nasal cavity, tooth pulp, and embryos (known as embryonic stem cells).

Dramatic improvements have been shown on some occasions, such as rats and mice regaining bladder control or the ability to walk after injury. While striking, such improvement often represents only a partial recovery. It holds significant promise, but is not direct evidence that such an approach will work in people, particularly those with more complex injuries.

The translation of findings from basic laboratory stem cell research to effective and safe treatments in the clinic involves many steps and challenges. It needs a firm scientific basis from animal studies and then careful evaluation in humans.

Many clinical studies examining stem cells for spinal repair are currently underway. The approaches fit broadly into two categories:

using stem cells as a source of cells to replace those damaged as a result of injury

applying cells to act on the bodys own cells to accelerate repair or prevent further damage.

One study that has attracted significant interest involves the injection of myelin-producing cells made from human embryonic stem cells. Researchers hoped that these cells, once injected into the spinal cord, would mature and form a new coating on the nerve cells, restoring the ability of signals to cross the spinal cord injury site. Preliminary results seem to show that the cells are safe; studies are ongoing.

Other clinical trials use cells from patients own bone marrow or adipose tissue (fat), or from donated cord blood or nerves from fetal tissue. The scientific rationale is based on the possibility that when transplanted into the injured spinal cord, these cells may provide surrounding tissue with protective factors which help to re-establish some of the connections important for the network of nerves that carry information around the body.

The field as it stands combines years of research, and tens of millions of dollars of investment. However, the development of stem cell therapies for spinal cord injury remains a long way from translating laboratory promise into proven and effective bedside treatments.

Each case is unique in people with spinal cord injury: the level of paralysis, and loss of sensation and function relate to the type of injury and its location. Injuries as a result of stab wounds or infection may result in different outcomes from those incurred as a result of trauma from a car accident or serious fall. The previous health of those injured, the care received at the time of injury, and the type of rehabilitation they access can all impact on subsequent health and mobility.

Such variability means caution needs to accompany claims of man walking again particularly when reports relate to a single individual.

In the case that was linked to the Australian of the Year award, the actual 2013 study focused on whether it was safe to take the patients own nerves and other cells from the nose and place these into the damaged region of the spine. While the researchers themselves recommended caution in interpreting the results, accompanying media reports focused on the outcome from just one of the six participants.

While the outcome was significant for the gentleman involved, we simply do not know whether recovery may have occurred for this individual even without stem cells, given the type of injury (stab wounds), the level of injury, the accompanying rehabilitation that he received or a combination of these factors. It cannot be assumed a similar outcome would be the case for all people with spinal injury.

Finding a way to alleviate the suffering of those with spinal cord injury, and many other conditions, drives the work of thousands of researchers and doctors around the globe. But stem cells are not a silver bullet and should not be immune from careful evaluation in clinical trials.

Failure to proceed with caution could actually cause harm. For example, a paraplegic woman who was also treated with nasal stem cells showed no clinical improvement, and developed a large mucus-secreting tumour in her spine. This case highlights the need for further refinement and assessment in properly conducted clinical trials before nasal stem cells can become part of mainstream medicine.

Its also worth noting that for spinal cord injury, trials for recovery of function are not limited to the use of stem cells but include approaches focused on promoting health of surviving nerves (neuroprotection), surgery following injury, nerve transfers, electrical stimulation, external physical supports known as exoskeletons, nanotechnology and brain-machine interfaces.

Ultimately, determining which of these approaches will improve the lives of people with spinal injury can only be done through rigorous, ethical research.

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Yes there's hope, but treating spinal injuries with stem cells is not a reality yet - The Conversation AU

Donating Bone Marrow | Cancer.Net

Bone marrow is a soft, spongy material found in your large bones. It makes more than 200 billion new blood cells every day, including red blood cells, white blood cells, and platelets. But for people with bone marrow disease, including several types of cancer, the process doesnt work properly. Often, a bone marrow transplant is a persons best chance of survival and a possible cure. The good news is that donating bone marrow can be as easy and painless as giving blood.

A bone marrow transplant replaces diseased bone marrow with healthy tissue, usually stem cells found in the blood. Thats why bone marrow transplants are also called stem cell transplants. In an allogeneic transplantation (ALLO transplant), blood stem cells from the bone marrow are transplanted from a donor into the patient. The donor stem cells can come from either the blood that circulates throughout another persons body or from umbilical cord blood.

But theres a catch. Before a person receives an ALLO transplant, a matching donor must be found using human leukocyte antigen (HLA) typing. This special blood test analyzes HLAs, which are specific proteins on the surface of white blood cells and other cells that make each persons tissue type unique. HLA-matched bone marrow is less likely to cause a possible side effect of transplantation called graft vs. host disease (GVHD). GVHD is when immune cells in the transplanted tissue recognize the recipients body as foreign and attack it.

Only about 30% of people who need a transplant can find an HLA-matched donor in their immediate family. For the remaining 70% of people, doctors need to find HLA-matched bone marrow from other donors. In 2016, that equals about 14,000 people from very young children up to older adults in the United States who need to find a donor outside of their close family.

The National Marrow Donor Program (NMDP) has a registry of potential donors that might be the match a patient needs. Heres how the donation process works:

You register with the NMDP online or in person at a donor center. You can find a center by calling the toll-free number 1-800-MARROW2.

You collect cells from your cheek with a cotton swab or provide a small blood sample. This is done by following directions in a mail-in kit or at a donor center. The sample is analyzed to determine your HLA type, which is recorded in the NMDP national database.

If an HLA match is made with a patient in need, the NMDP contacts you. A donor center takes a new sample of your blood, which is sent to the patients transplant center to confirm the HLA match. Once doctors confirm the match, youd meet with a counselor from the NMDP to talk about the procedures, benefits, and risks of the donation process. You then decide whether youre comfortable with donating.

If you agree to donate bone marrow, youll likely do whats called a peripheral blood stem cell (PBSC) collection. Heres how it works:

For 5 days leading up to the donation, youll get a daily 5-minute injection of granulocyte colony-stimulating factor (G-CSF), a white blood cell growth hormone.

On day 5, a trained health care provider will place a needle in each of your arms. One needle will remove blood, and a machine circulates the blood and collects the stem cells. Your blood then is returned to your body through the second needle. The process takes about 3 hours and may be repeated on a second donation day. Side effects include headaches, bone soreness, and discomfort from the needles during the process.

Although less common, some donors may be asked to undergo a bone marrow harvest, during which doctors take bone marrow from the back of a donors hip bone during surgery. Donors usually go home the same day of the surgery and can return to normal activity within 1 week. Common side effects include nausea, headache, and fatigue, most often related to the anesthesia. Bruising or discomfort in the lower back is also common.

The end result? You could help cure someones disease.

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Donating Bone Marrow | Cancer.Net

Bone Marrow Transplantation | Hematology and Oncology

What is a bone marrow transplant?

Bone marrow transplant (BMT) is a special therapy for patients with certain cancers or other diseases. A bone marrow transplant involves taking cells that are normally found in the bone marrow (stem cells), filtering those cells, and giving them back either to the donor (patient) or to another person. The goal of BMT is to transfuse healthy bone marrow cells into a person after their own unhealthy bone marrow has been treated to kill the abnormal cells.

Bone marrow transplant has been used successfully to treat diseases such as leukemias, lymphomas, aplastic anemia, immune deficiency disorders, and some solid tumor cancers since 1968.

What is bone marrow?

Bone marrow is the soft, spongy tissue found inside bones. It is the medium for development and storage of most of the body's blood cells.

The blood cells that produce other blood cells are called stem cells. The most primitive of the stem cells is called the pluripotent stem cell, which is different than other blood cells with regards to the following properties:

It is the stem cells that are needed in bone marrow transplant.

Why is a bone marrow transplant needed?

The goal of a bone marrow transplant is to cure many diseases and types of cancer. When the doses of chemotherapy or radiation needed to cure a cancer are so high that a person's bone marrow stem cells will be permanently damaged or destroyed by the treatment, a bone marrow transplant may be needed. Bone marrow transplants may also be needed if the bone marrow has been destroyed by a disease.

A bone marrow transplant can be used to:

The risks and benefits must be weighed in a thorough discussion with your doctor and specialists in bone marrow transplants prior to procedure.

What are some diseases that may benefit from bone marrow transplant?

The following diseases are the ones that most commonly benefit from bone marrow transplant:

However, patients experience diseases differently, and bone marrow transplant may not be appropriate for everyone who suffers from these diseases.

What are the different types of bone marrow transplants?

There are different types of bone marrow transplants depending on who the donor is. The different types of BMT include the following:

How are a donor and recipient matched?

Matching involves typing human leukocyte antigen (HLA) tissue. The antigens on the surface of these special white blood cells determine the genetic makeup of a person's immune system. There are at least 100 HLA antigens; however, it is believed that there are a few major antigens that determine whether a donor and recipient match. The others are considered "minor" and their effect on a successful transplant is not as well-defined.

Medical research is still investigating the role all antigens play in the process of a bone marrow transplant. The more antigens that match, the better the engraftment of donated marrow. Engraftment of the stem cells occurs when the donated cells make their way to the marrow and begin producing new blood cells.

Most of the genes that "code" for the human immune system are on one chromosome. Since we only have two of each chromosome, one we received from each of our parents, a full sibling of a patient in need of a transplant has a one in four chance of having gotten the same set of chromosomes and being a "full match" for transplantation.

The bone marrow transplant team

The group of specialists involved in the care of patients going through transplant is often referred to as the transplant team. All individuals work together to provide the best chance for a successful transplant. The team consists of the following:

An extensive evaluation is completed by the bone marrow transplant team. The decision for you to undergo a bone marrow transplant will be based on many factors, including the following:

For a patient receiving the transplant, the following will occur in advance of the procedure:

Preparation for the donor

How are the stem cells collected?

A bone marrow transplant is done by transferring stem cells from one person to another. Stem cells can either be collected from the circulating cells in the blood (the peripheral system) or from the bone marrow.

If the donor is the person himself or herself, it is called an autologous bone marrow transplant. If an autologous transplant is planned, previously collected stem cells, from either peripheral (apheresis) or harvest, are counted, screened, and ready to infuse.

The bone marrow transplant procedure

The preparations for a bone marrow transplant vary depending on the type of transplant, the disease requiring transplant, and your tolerance for certain medications. Consider the following:

The days before transplant are counted as minus days. The day of transplant is considered day zero. Engraftment and recovery following the transplant are counted as plus days. For example, a patient may enter the hospital on day -8 for preparative regimen. The day of transplant is numbered zero. Days +1, +2, etc., will follow. There are specific events, complications, and risks associated with each day before, during, and after transplant. The days are numbered to help the patient and family understand where they are in terms of risks and discharge planning.

During infusion of bone marrow, the patient may experience the following:

After infusion, the patient may:

After leaving the hospital, the recovery process continues for several months or longer, during which time the patient cannot return to work or many previously enjoyed activities. The patient must also make frequent follow-up visits to the hospital or doctor's office.

When does engraftment occur?

Engraftment of the stem cells occurs when the donated cells make their way to the marrow and begin producing new blood cells. Depending on the type of transplant and the disease being treated, engraftment usually occurs around day +15 or +30. Blood counts will be checked frequently during the days following transplant to evaluate initiation and progress of engraftment. Platelets are generally the last blood cell to recover.

Engraftment can be delayed because of infection, medications, low donated stem cell count, or graft failure. Although the new bone marrow may begin making cells in the first 30 days following transplant, it may take months, even years, for the entire immune system to fully recover.

What complications and side effects may occur following BMT?

Complications may vary, depending on the following:

The following are complications that may occur with a bone marrow transplant. However, each individual may experience symptoms differently. These complications may also occur alone, or in combination:

Long-term outlook for a bone marrow transplantation

Prognosis greatly depends on the following:

As with any procedure, in bone marrow transplant the prognosis and long-term survival can vary greatly from person to person. The number of transplants being done for an increasing number of diseases, as well as ongoing medical developments, have greatly improved the outcome for bone marrow transplant in children and adults. Continuous follow-up care is essential for the patient following a bone marrow transplant. New methods to improve treatment and to decrease complications and side effects of a bone marrow transplant are continually being discovered.

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Bone Marrow Transplantation | Hematology and Oncology

Bone – Wikipedia

A bone is a rigid organ that constitutes part of the vertebral skeleton. Bones support and protect the various organs of the body, produce red and white blood cells, store minerals and also enable mobility as well as support for the body. Bone tissue is a type of dense connective tissue. Bones come in a variety of shapes and sizes and have a complex internal and external structure. They are lightweight yet strong and hard, and serve multiple functions. Mineralized osseous tissue, or bone tissue, is of two types, cortical and cancellous, and gives a bone rigidity and a coral-like three-dimensional internal structure. Other types of tissue found in bones include marrow, endosteum, periosteum, nerves, blood vessels and cartilage.

Bone is an active tissue composed of different types of bone cells. Osteoblasts and osteocytes are involved in the creation and mineralisation of bone; osteoclasts are involved in the reabsorption of bone tissue. The mineralised matrix of bone tissue has an organic component of mainly collagen called ossein and an inorganic component of bone mineral made up of various salts.

In the human body at birth, there are over 270 bones,[1] but many of these fuse together during development, leaving a total of 206 separate bones in the adult,[2] not counting numerous small sesamoid bones. The largest bone in the body is the thigh-bone (femur) and the smallest is the stapes in the middle ear.

Bone is not a uniformly solid material, but is mostly a matrix. The primary tissue of bone, bone tissue (osseous tissue), is relatively hard and lightweight. Its matrix is mostly made up of a composite material incorporating the inorganic mineral calcium phosphate in the chemical arrangement termed calcium hydroxylapatite (this is the bone mineral that gives bones their rigidity) and collagen, an elastic protein which improves fracture resistance.[3] Bone is formed by the hardening of this matrix around entrapped cells. When these cells become entrapped from osteoblasts they become osteocytes.[citation needed]

The hard outer layer of bones is composed of cortical bone also called compact bone. Cortical referring to the outer (cortex) layer. The hard outer layer gives bone its smooth, white, and solid appearance, and accounts for 80% of the total bone mass of an adult human skeleton.[citation needed] However, that proportion may be much lower, especially in marine mammals and marine turtles, or in various Mesozoic marine reptiles, such as ichthyosaurs,[4] among others.[5]

Cortical bone consists of multiple microscopic columns, each called an osteon. Each column is multiple layers of osteoblasts and osteocytes around a central canal called the Haversian canal. Volkmann's canals at right angles connect the osteons together. The columns are metabolically active, and as bone is reabsorbed and created the nature and location of the cells within the osteon will change. Cortical bone is covered by a periosteum on its outer surface, and an endosteum on its inner surface. The endosteum is the boundary between the cortical bone and the cancellous bone.

Filling the interior of the bone is the cancellous bone also known as trabecular or spongy bone tissue. It is an open cell porous network. Thin formations of osteoblasts covered in endosteum create an irregular network of spaces. Within these spaces are bone marrow and hematopoietic stem cells that give rise to platelets, red blood cells and white blood cells. Trabecular marrow is composed of a network of rod- and plate-like elements that make the overall organ lighter and allow room for blood vessels and marrow. Trabecular bone accounts for the remaining 20% of total bone mass but has nearly ten times the surface area of compact bone.[8]

Bone marrow, also known as myeloid tissue, can be found in almost any bone that holds cancellous tissue. In newborns, all such bones are filled exclusively with red marrow, but as the child ages it is mostly replaced by yellow, or fatty marrow. In adults, red marrow is mostly found in the bone marrow of the femur, the ribs, the vertebrae and pelvic bones.[citation needed]

Bone is a metabolically active tissue composed of several types of cells. These cells include osteoblasts, which are involved in the creation and mineralization of bone tissue, osteocytes, and osteoclasts, which are involved in the reabsorption of bone tissue. Osteoblasts and osteocytes are derived from osteoprogenitor cells, but osteoclasts are derived from the same cells that differentiate to form macrophages and monocytes. Within the marrow of the bone there are also hematopoietic stem cells. These cells give rise to other cells, including white blood cells, red blood cells, and platelets.

Bones consist of living cells embedded in a mineralized organic matrix. This matrix consists of organic components, mainly collagen "organic" referring to materials produced as a result of the human body and inorganic components, primarily hydroxyapatite and other salts of calcium and phosphate. Above 30% of the acellular part of bone consists of the organic components, and 70% of salts. The strands of collagen give bone its tensile strength, and the interspersed crystals of hydroxyapatite give bone its compressional strength. These effects are synergistic.

The inorganic composition of bone (bone mineral) is primarily formed from salts of calcium and phosphate, the major salt being hydroxyapatite (Ca10(PO4)6(OH)2). The exact composition of the matrix may change over time and with nutrition, with the ratio of calcium to phosphate varying between 1.3 and 2.0 (per weight), and trace minerals such as magnesium, sodium, potassium and carbonate also being found.

The organic part of matrix is mainly composed of Type I collagen. Collagen composes 9095% of the organic matrix, with remainder of the matrix being a homogenous liquid called ground substance consisting of proteoglycans such as hyaluronic acid and chondroitin sulfate. Collagen consists of strands of repeating units, which give bone tensile strength, and are arranged in an overlapping fashion that prevents shear stress. The function of ground substance is not fully known. Two types of bone can be identified microscopically according to the arrangement of collagen:

Woven bone is produced when osteoblasts produce osteoid rapidly, which occurs initially in all fetal bones, but is later replaced by more resilient lamellar bone. In adults woven bone is created after fractures or in Paget's disease. Woven bone is weaker, with a smaller number of randomly oriented collagen fibers, but forms quickly; it is for this appearance of the fibrous matrix that the bone is termed woven. It is soon replaced by lamellar bone, which is highly organized in concentric sheets with a much lower proportion of osteocytes to surrounding tissue. Lamellar bone, which makes its first appearance in humans in the fetus during the third trimester,[16] is stronger and filled with many collagen fibers parallel to other fibers in the same layer (these parallel columns are called osteons). In cross-section, the fibers run in opposite directions in alternating layers, much like in plywood, assisting in the bone's ability to resist torsion forces. After a fracture, woven bone forms initially and is gradually replaced by lamellar bone during a process known as "bony substitution." Compared to woven bone, lamellar bone formation takes place more slowly. The orderly deposition of collagen fibers restricts the formation of osteoid to about 1 to 2m per day. Lamellar bone also requires a relatively flat surface to lay the collagen fibers in parallel or concentric layers.[citation needed]

The extracellular matrix of bone is laid down by osteoblasts, which secrete both collagen and ground substance. These synthesise collagen within the cell, and then secrete collagen fibrils. The collagen fibres rapidly polymerise to form collagen strands. At this stage they are not yet mineralised, and are called "osteoid". Around the strands calcium and phosphate precipitate on the surface of these strands, within a days to weeks becoming crystals of hydroxyapatite.

In order to mineralise the bone, the osteoblasts secrete vesicles containing alkaline phosphatase. This cleaves the phosphate groups and acts as the foci for calcium and phosphate deposition. The vesicles then rupture and act as a centre for crystals to grow on. More particularly, bone mineral is formed from globular and plate structures.[17][18]

There are five types of bones in the human body: long, short, flat, irregular, and sesamoid.[19]

In the study of anatomy, anatomists use a number of anatomical terms to describe the appearance, shape and function of bones. Other anatomical terms are also used to describe the location of bones. Like other anatomical terms, many of these derive from Latin and Greek. Some anatomists still use Latin to refer to bones. The term "osseous", and the prefix "osteo-", referring to things related to bone, are still used commonly today.

Some examples of terms used to describe bones include the term "foramen" to describe a hole through which something passes, and a "canal" or "meatus" to describe a tunnel-like structure. A protrusion from a bone can be called a number of terms, including a "condyle", "crest", "spine", "eminence", "tubercle" or "tuberosity", depending on the protrusion's shape and location. In general, long bones are said to have a "head", "neck", and "body".

When two bones join together, they are said to "articulate". If the two bones have a fibrous connection and are relatively immobile, then the joint is called a "suture".

The formation of bone is called ossification. During the fetal stage of development this occurs by two processes, Intramembranous ossification and endochondral ossification.[citation needed] Intramembranous ossification involves the creation of bone from connective tissue, whereas in the process of endochondral ossification bone is created from cartilage.

Intramembranous ossification mainly occurs during formation of the flat bones of the skull but also the mandible, maxilla, and clavicles; the bone is formed from connective tissue such as mesenchyme tissue rather than from cartilage. The steps in intramembranous ossification are:[citation needed]

Endochondral ossification, on the other hand, occurs in long bones and most of the rest of the bones in the body; it involves an initial hyaline cartilage that continues to grow. The steps in endochondral ossification are:[citation needed]

Endochondral ossification begins with points in the cartilage called "primary ossification centers." They mostly appear during fetal development, though a few short bones begin their primary ossification after birth. They are responsible for the formation of the diaphyses of long bones, short bones and certain parts of irregular bones. Secondary ossification occurs after birth, and forms the epiphyses of long bones and the extremities of irregular and flat bones. The diaphysis and both epiphyses of a long bone are separated by a growing zone of cartilage (the epiphyseal plate). When the child reaches skeletal maturity (18 to 25 years of age), all of the cartilage is replaced by bone, fusing the diaphysis and both epiphyses together (epiphyseal closure).[citation needed] In the upper limbs, only the diaphyses of the long bones and scapula are ossified. The epiphyses, carpal bones, coracoid process, medial border of the scapula, and acromion are still cartilaginous.[21]

The following steps are followed in the conversion of cartilage to bone:

Bones have a variety of functions:

Bones serve a variety of mechanical functions. Together the bones in the body form the skeleton. They provide a frame to keep the body supported, and an attachment point for skeletal muscles, tendons, ligaments and joints, which function together to generate and transfer forces so that individual body parts or the whole body can be manipulated in three-dimensional space (the interaction between bone and muscle is studied in biomechanics).

Bones protect internal organs, such as the skull protecting the brain or the ribs protecting the heart and lungs. Because of the way that bone is formed, bone has a high compressive strength of about 170 MPa (1800 kgf/cm),[3] poor tensile strength of 104121 MPa, and a very low shear stress strength (51.6 MPa).[23][24] This means that bone resists pushing(compressional) stress well, resist pulling(tensional) stress less well, but only poorly resists shear stress (such as due to torsional loads). While bone is essentially brittle, bone does have a significant degree of elasticity, contributed chiefly by collagen. The macroscopic yield strength of cancellous bone has been investigated using high resolution computer models.[25]

Mechanically, bones also have a special role in hearing. The ossicles are three small bones in the middle ear which are involved in sound transduction.

Cancellous bones contain bone marrow. Bone marrow produces blood cells in a process called hematopoiesis.[26] Blood cells that are created in bone marrow include red blood cells, platelets and white blood cells. Progenitor cells such as the hematopoietic stem cell divide in a process called mitosis to produce precursor cells. These include precursors which eventually give rise to white blood cells, and erythroblasts which give rise to red blood cells. Unlike red and white blood cells, created by mitosis, platelets are shed from very large cells called megakaryocytes. This process of progressive differentiation occurs within the bone marrow. After the cells are matured, they enter the circulation. Every day, over 2.5 billion red blood cells and platelets, and 50100 billion granulocytes are produced in this way.

As well as creating cells, bone marrow is also one of the major sites where defective or aged red blood cells are destroyed.

Bone is constantly being created and replaced in a process known as remodeling. This ongoing turnover of bone is a process of resorption followed by replacement of bone with little change in shape. This is accomplished through osteoblasts and osteoclasts. Cells are stimulated by a variety of signals, and together referred to as a remodeling unit. Approximately 10% of the skeletal mass of an adult is remodelled each year.[32] The purpose of remodeling is to regulate calcium homeostasis, repair microdamaged bones from everyday stress, and also to shape and sculpt the skeleton during growth.[citation needed]. Repeated stress, such as weight-bearing exercise or bone healing, results in the bone thickening at the points of maximum stress (Wolff's law). It has been hypothesized that this is a result of bone's piezoelectric properties, which cause bone to generate small electrical potentials under stress.[33]

The action of osteoblasts and osteoclasts are controlled by a number of chemical enzymes that either promote or inhibit the activity of the bone remodeling cells, controlling the rate at which bone is made, destroyed, or changed in shape. The cells also use paracrine signalling to control the activity of each other.[citation needed] For example, the rate at which osteoclasts resorb bone is inhibited by calcitonin and osteoprotegerin. Calcitonin is produced by parafollicular cells in the thyroid gland, and can bind to receptors on osteoclasts to directly inhibit osteoclast activity. Osteoprotegerin is secreted by osteoblasts and is able to bind RANK-L, inhibiting osteoclast stimulation.[34]

Osteoblasts can also be stimulated to increase bone mass through increased secretion of osteoid and by inhibiting the ability of osteoclasts to break down osseous tissue.[citation needed] Increased secretion of osteoid is stimulated by the secretion of growth hormone by the pituitary, thyroid hormone and the sex hormones (estrogens and androgens). These hormones also promote increased secretion of osteoprotegerin.[34] Osteoblasts can also be induced to secrete a number of cytokines that promote reabsorbtion of bone by stimulating osteoclast activity and differentiation from progenitor cells. Vitamin D, parathyroid hormone and stimulation from osteocytes induce osteoblasts to increase secretion of RANK-ligand and interleukin 6, which cytokines then stimulate increased reabsorption of bone by osteoclasts. These same compounds also increase secretion of macrophage colony-stimulating factor by osteoblasts, which promotes the differentiation of progenitor cells into osteoclasts, and decrease secretion of osteoprotegerin.[citation needed]

Bone volume is determined by the rates of bone formation and bone resorption. Recent research has suggested that certain growth factors may work to locally alter bone formation by increasing osteoblast activity. Numerous bone-derived growth factors have been isolated and classified via bone cultures. These factors include insulin-like growth factors I and II, transforming growth factor-beta, fibroblast growth factor, platelet-derived growth factor, and bone morphogenetic proteins.[35] Evidence suggests that bone cells produce growth factors for extracellular storage in the bone matrix. The release of these growth factors from the bone matrix could cause the proliferation of osteoblast precursors. Essentially, bone growth factors may act as potential determinants of local bone formation.[35] Research has suggested that trabecular bone volume in postemenopausal osteoporosis may be determined by the relationship between the total bone forming surface and the percent of surface resorption.[36]

A number of diseases can affect bone, including arthritis, fractures, infections, osteoporosis and tumours. Conditions relating to bone can be managed by a variety of doctors, including rheumatologists for joints, and orthopedic surgeons, who may conduct surgery to fix broken bones. Other doctors, such as rehabilitation specialists may be involved in recovery, radiologists in interpreting the findings on imaging, and pathologists in investigating the cause of the disease, and family doctors may play a role in preventing complications of bone disease such as osteoporosis.

When a doctor sees a patient, a history and exam will be taken. Bones are then often imaged, called radiography. This might include ultrasound X-ray, CT scan, MRI scan and other imaging such as a Bone scan, which may be used to investigate cancer. Other tests such as a blood test for autoimmune markers may be taken, or a synovial fluid aspirate may be taken.

In normal bone, fractures occur when there is significant force applied, or repetitive trauma over a long time. Fractures can also occur when a bone is weakened, such as with osteoporosis, or when there is a structural problem, such as when the bone remodels excessively (such as Paget's disease) or is the site of the growth of cancer. Common fractures include wrist fractures and hip fractures, associated with osteoporosis, vertebral fractures associated with high-energy trauma and cancer, and fractures of long-bones. Not all fractures are painful. When serious, depending on the fractures type and location, complications may include flail chest, compartment syndromes or fat embolism. Compound fractures involve the bone's penetration through the skin.

Fractures and their underlying causes can be investigated by X-rays, CT scans and MRIs. Fractures are described by their location and shape, and several classification systems exist, depending on the location of the fracture. A common long bone fracture in children is a SalterHarris fracture.[39] When fractures are managed, pain relief is often given, and the fractured area is often immobilised. This is to promote bone healing. In addition, surgical measures such as internal fixation may be used. Because of the immobilisation, people with fractures are often advised to undergo rehabilitation.

There are several types of tumour that can affect bone; examples of benign bone tumours include osteoma, osteoid osteoma, osteochondroma, osteoblastoma, enchondroma, giant cell tumor of bone, aneurysmal bone cyst, and fibrous dysplasia of bone.

Cancer can arise in bone tissue, and bones are also a common site for other cancers to spread (metastasise) to. Cancers that arise in bone are called "primary" cancers, although such cancers are rare. Metastases within bone are "secondary" cancers, with the most common being breast cancer, lung cancer, prostate cancer, thyroid cancer, and kidney cancer. Secondary cancers that affect bone can either destroy bone (called a "lytic" cancer) or create bone (a "sclerotic" cancer). Cancers of the bone marrow inside the bone can also affect bone tissue, examples including leukemia and multiple myeloma. Bone may also be affected by cancers in other parts of the body. Cancers in other parts of the body may release parathyroid hormone or parathyroid hormone-related peptide. This increases bone reabsorption, and can lead to bone fractures.

Bone tissue that is destroyed or altered as a result of cancers is distorted, weakened, and more prone to fracture. This may lead to compression of the spinal cord, destruction of the marrow resulting in bruising, bleeding and immunosuppression, and is one cause of bone pain. If the cancer is metastatic, then there might be other symptoms depending on the site of the original cancer. Some bone cancers can also be felt.

Cancers of the bone are managed according to their type, their stage, prognosis, and what symptoms they cause. Many primary cancers of bone are treated with radiotherapy. Cancers of bone marrow may be treated with chemotherapy, and other forms of targeted therapy such as immunotherapy may be used.Palliative care, which focuses on maximising a person's quality of life, may play a role in management, particularly if the likelihood of survival within five years is poor.

Osteoporosis is a disease of bone where there is reduced bone mineral density, increasing the likelihood of fractures. Osteoporosis is defined by the World Health Organization in women as a bone mineral density 2.5 standard deviations below peak bone mass, relative to the age and sex-matched average, as measured by Dual energy X-ray absorptiometry, with the term "established osteoporosis" including the presence of a fragility fracture.[43] Osteoporosis is most common in women after menopause, when it is called "postmenopausal osteoporosis", but may develop in men and premenopausal women in the presence of particular hormonal disorders and other chronic diseases or as a result of smoking and medications, specifically glucocorticoids. Osteoporosis usually has no symptoms until a fracture occurs. For this reason, DEXA scans are often done in people with one or more risk factors, who have developed osteoporosis and be at risk of fracture.

Osteoporosis treatment includes advice to stop smoking, decrease alcohol consumption, exercise regularly, and have a healthy diet. Calcium supplements may also be advised, as may Vitamin D. When medication is used, it may include bisphosphonates, Strontium ranelate, and osteoporosis may be one factor considered when commencing Hormone replacement therapy.[44]

The study of bones and teeth is referred to as osteology. It is frequently used in anthropology, archeology and forensic science for a variety of tasks. This can include determining the nutritional, health, age or injury status of the individual the bones were taken from. Preparing fleshed bones for these types of studies can involve the process of maceration.

Typically anthropologists and archeologists study bone tools made by Homo sapiens and Homo neanderthalensis. Bones can serve a number of uses such as projectile points or artistic pigments, and can also be made from external bones such as antlers.

Bird skeletons are very lightweight. Their bones are smaller and thinner, to aid flight. Among mammals, bats come closest to birds in terms of bone density, suggesting that small dense bones are a flight adaptation. Many bird bones have little marrow due to their being hollow.[45]

A bird's beak is primarily made of bone as projections of the mandibles which are covered in keratin.

A deer's antlers are composed of bone which is an unusual example of bone being outside the skin of the animal once the velvet is shed.[46]

The extinct predatory fish Dunkleosteus had sharp edges of hard exposed bone along its jaws.[citation needed]

Many animals possess an exoskeleton that is not made of bone, These include insects and crustaceans.

Bones from slaughtered animals have a number of uses. In prehistoric times, they have been used for making bone tools. They have further been used in bone carving, already important in prehistoric art, and also in modern time as crafting materials for buttons, beads, handles, bobbins, calculation aids, head nuts, dice, poker chips, pick-up sticks, ornaments, etc. A special genre is scrimshaw.

Bone glue can be made by prolonged boiling of ground or cracked bones, followed by filtering and evaporation to thicken the resulting fluid. Historically once important, bone glue and other animal glues today have only a few specialized uses, such as in antiques restoration. Essentially the same process, with further refinement, thickening and drying, is used to make gelatin.

Broth is made by simmering several ingredients for a long time, traditionally including bones.

Ground bones are used as an organic phosphorus-nitrogen fertilizer and as additive in animal feed. Bones, in particular after calcination to bone ash, are used as source of calcium phosphate for the production of bone china and previously also phosphorus chemicals.[citation needed]

Bone char, a porous, black, granular material primarily used for filtration and also as a black pigment, is produced by charring mammal bones.

Oracle bone script was a writing system used in Ancient china based on inscriptions in bones.

To point the bone at someone is considered bad luck in some cultures, such as Australian aborigines, such as by the Kurdaitcha.

Osteopathic medicine is a school of medical thought originally developed based on the idea of the link between the musculoskeletal system and overall health, but now very similar to mainstream medicine. As of 2012[update], over 77,000 physicians in the United States are trained in Osteopathic medicine colleges.[47]

The wishbones of fowl have been used for divination, and are still customarily used in a tradition to determine which one of two people pulling on either prong of the bone may make a wish.

Various cultures throughout history have adopted the custom of shaping an infant's head by the practice of artificial cranial deformation. A widely practised custom in China was that of foot binding to limit the normal growth of the foot.

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Bone - Wikipedia

Stem cells from fat outperform those from bone marrow in …

Durham, NC A new study appearing in the current issue of STEM CELLS Translational Medicine indicates that stem cells harvested from fat (adipose) are more potent than those collected from bone marrow in helping to modulate the bodys immune system.

The finding could have significant implications in developing new stem-cell-based therapies, as adipose tissue-derived stem cells (AT-SCs) are far more plentiful in the body than those found in bone marrow and can be collected from waste material from liposuction procedures. Stem cells are considered potential therapies for a range of conditions, from enhancing skin graft survival to treating inflammatory bowel disease.

Researchers at the Leiden University Medical Centers Department of Immunohematology and Blood Transfusion in Leiden, The Netherlands, led by Helene Roelofs, Ph.D., conducted the study. They were seeking an alternative to bone marrow for stem cell therapies because of the low number of stem cells available in marrow and also because harvesting them involves an invasive procedure.

Adipose tissue is an interesting alternative since it contains approximately a 500-fold higher frequency of stem cells and tissue collection is simple, Dr. Roelofs said.

Moreover, Dr. Sara M. Melief added, 400,000 liposuctions a year are performed in the U.S. alone, where the aspirated adipose tissue is regarded as waste and could be collected without any additional burden or risk for the donor.

For the study, the team used stem cells collected from the bone marrow and fat tissue of age-matched donors. They compared the cells ability to regulate the immune system in vitro and found that the two performed similarly, although it took a smaller dose for the AT-SCs to achieve the same effect on the immune cells.

When it came to secreting cytokines the cell signaling molecules that regulate the immune system the AT-SCs also outperformed the bone marrow-derived cells.

This all adds up to make AT-SC a good alternative to bone marrow stem cells for developing new therapies, Dr. Roelofs concluded.

Cells from bone marrow and from fat were equivalent in terms of their potential to differentiate into multiple cell types, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of Wake Forest Institute for Regenerative Medicine. The fact that the cells from fat tissue seem to be more potent at suppressing the immune system suggest their promise in clinical therapies.

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Stem cells from fat outperform those from bone marrow in ...

Stem-cell therapy – Wikipedia

This article is about the medical therapy. For the cell type, see Stem cell.

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition.

Bone marrow transplant is the most widely used stem-cell therapy, but some therapies derived from umbilical cord blood are also in use. Research is underway to develop various sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes, heart disease, and other conditions.

Stem-cell therapy has become controversial following developments such as the ability of scientists to isolate and culture embryonic stem cells, to create stem cells using somatic cell nuclear transfer and their use of techniques to create induced pluripotent stem cells. This controversy is often related to abortion politics and to human cloning. Additionally, efforts to market treatments based on transplant of stored umbilical cord blood have been controversial.

For over 30 years, bone marrow has been used to treat cancer patients with conditions such as leukaemia and lymphoma; this is the only form of stem-cell therapy that is widely practiced.[1][2][3] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem-cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment. The transplanted cells also generate an immune response that helps to kill off the cancer cells; this process can go too far, however, leading to graft vs host disease, the most serious side effect of this treatment.[4]

Another stem-cell therapy called Prochymal, was conditionally approved in Canada in 2012 for the management of acute graft-vs-host disease in children who are unresponsive to steroids.[5] It is an allogenic stem therapy based on mesenchymal stem cells (MSCs) derived from the bone marrow of adult donors. MSCs are purified from the marrow, cultured and packaged, with up to 10,000 doses derived from a single donor. The doses are stored frozen until needed.[6]

The FDA has approved five hematopoietic stem-cell products derived from umbilical cord blood, for the treatment of blood and immunological diseases.[7]

In 2014, the European Medicines Agency recommended approval of Holoclar, a treatment involving stem cells, for use in the European Union. Holoclar is used for people with severe limbal stem cell deficiency due to burns in the eye.[8]

In March 2016 GlaxoSmithKline's Strimvelis (GSK2696273) therapy for the treatment ADA-SCID was recommended for EU approval.[9]

Stem cells are being studied for a number of reasons. The molecules and exosomes released from stem cells are also being studied in an effort to make medications.[10]

Research has been conducted on the effects of stem cells on animal models of brain degeneration, such as in Parkinson's, Amyotrophic lateral sclerosis, and Alzheimer's disease.[11][12][13] There have been preliminary studies related to multiple sclerosis.[14][15]

Healthy adult brains contain neural stem cells which divide to maintain general stem-cell numbers, or become progenitor cells. In healthy adult laboratory animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Pharmacological activation of endogenous neural stem cells has been reported to induce neuroprotection and behavioral recovery in adult rat models of neurological disorder.[16][17][18]

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. A small clinical trial was underway in Scotland in 2013, in which stem cells were injected into the brains of stroke patients.[19]

Clinical and animal studies have been conducted into the use of stem cells in cases of spinal cord injury.[20][21][22]

The pioneering work[23] by Bodo-Eckehard Strauer has now been discredited by the identification of hundreds of factual contradictions.[24] Among several clinical trials that have reported that adult stem-cell therapy is safe and effective, powerful effects have been reported from only a few laboratories, but this has covered old[25] and recent[26] infarcts as well as heart failure not arising from myocardial infarction.[27] While initial animal studies demonstrated remarkable therapeutic effects,[28][29] later clinical trials achieved only modest, though statistically significant, improvements.[30][31] Possible reasons for this discrepancy are patient age,[32] timing of treatment[33] and the recent occurrence of a myocardial infarction.[34] It appears that these obstacles may be overcome by additional treatments which increase the effectiveness of the treatment[35] or by optimizing the methodology although these too can be controversial. Current studies vary greatly in cell-procuring techniques, cell types, cell-administration timing and procedures, and studied parameters, making it very difficult to make comparisons. Comparative studies are therefore currently needed.

Stem-cell therapy for treatment of myocardial infarction usually makes use of autologous bone-marrow stem cells (a specific type or all), however other types of adult stem cells may be used, such as adipose-derived stem cells.[36] Adult stem cell therapy for treating heart disease was commercially available in at least five continents as of 2007.[citation needed]

Possible mechanisms of recovery include:[11]

It may be possible to have adult bone-marrow cells differentiate into heart muscle cells.[11]

The first successful integration of human embryonic stem cell derived cardiomyocytes in guinea pigs (mouse hearts beat too fast) was reported in August 2012. The contraction strength was measured four weeks after the guinea pigs underwent simulated heart attacks and cell treatment. The cells contracted synchronously with the existing cells, but it is unknown if the positive results were produced mainly from paracrine as opposed to direct electromechanical effects from the human cells. Future work will focus on how to get the cells to engraft more strongly around the scar tissue. Whether treatments from embryonic or adult bone marrow stem cells will prove more effective remains to be seen.[37]

In 2013 the pioneering reports of powerful beneficial effects of autologous bone marrow stem cells on ventricular function were found to contain "hundreds" of discrepancies.[38] Critics report that of 48 reports there seemed to be just five underlying trials, and that in many cases whether they were randomized or merely observational accepter-versus-rejecter, was contradictory between reports of the same trial. One pair of reports of identical baseline characteristics and final results, was presented in two publications as, respectively, a 578 patient randomized trial and as a 391 patient observational study. Other reports required (impossible) negative standard deviations in subsets of patients, or contained fractional patients, negative NYHA classes. Overall there were many more patients published as having receiving stem cells in trials, than the number of stem cells processed in the hospital's laboratory during that time. A university investigation, closed in 2012 without reporting, was reopened in July 2013.[39]

One of the most promising benefits of stem cell therapy is the potential for cardiac tissue regeneration to reverse the tissue loss underlying the development of heart failure after cardiac injury.[40]

Initially, the observed improvements were attributed to a transdifferentiation of BM-MSCs into cardiomyocyte-like cells.[28] Given the apparent inadequacy of unmodified stem cells for heart tissue regeneration, a more promising modern technique involves treating these cells to create cardiac progenitor cells before implantation to the injured area.[41]

The specificity of the human immune-cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are diagnosed and classified via a subspecialty of pathology known as hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.[citation needed]

Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red-blood-cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells.[42] Further research into this technique should have potential benefits to gene therapy, blood transfusion, and topical medicine.

In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice[43] and were able to grow bioengineered teeth stand-alone in the laboratory. Researchers are confident that the tooth regeneration technology can be used to grow live teeth in human patients.

In theory, stem cells taken from the patient could be coaxed in the lab turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to be grown in a time over three weeks.[44] It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth. Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.[45][46]

Research is ongoing in different fields, alligators which are polyphyodonts grow up to 50 times a successional tooth (a small replacement tooth) under each mature functional tooth for replacement once a year.[47]

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.[48]

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable." When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.[49] The latest such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.[50]

In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant was a cornea transplant. The absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.

The University Hospital of New Jersey reports that the success rate for growth of new cells from transplanted stem cells varies from 25 percent to 70 percent.[51]

In 2014, researchers demonstrated that stem cells collected as biopsies from donor human corneas can prevent scar formation without provoking a rejection response in mice with corneal damage.[52]

In January 2012, The Lancet published a paper by Steven Schwartz, at UCLA's Jules Stein Eye Institute, reporting two women who had gone legally blind from macular degeneration had dramatic improvements in their vision after retinal injections of human embryonic stem cells.[53]

In June 2015, the Stem Cell Ophthalmology Treatment Study (SCOTS), the largest adult stem cell study in ophthalmology ( NCT # 01920867) published initial results on a patient with optic nerve disease who improved from 20/2000 to 20/40 following treatment with bone marrow derived stem cells.[54]

Diabetes patients lose the function of insulin-producing beta cells within the pancreas.[55] In recent experiments, scientists have been able to coax embryonic stem cell to turn into beta cells in the lab. In theory if the beta cell is transplanted successfully, they will be able to replace malfunctioning ones in a diabetic patient.[56]

Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.

However, clinical success is highly dependent on the development of the following procedures:[11]

Clinical case reports in the treatment orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects.[57][58] The results of trials that include a large number of subjects, are yet to be published. However, a published safety study conducted in a group of 227 patients over a 3-4-year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation.[59]

Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[60]

Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells.[61] A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation.[61] Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.[61]

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.[62]

Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed.[63] It could potentially treat azoospermia.

In 2012, oogonial stem cells were isolated from adult mouse and human ovaries and demonstrated to be capable of forming mature oocytes.[64] These cells have the potential to treat infertility.

Destruction of the immune system by the HIV is driven by the loss of CD4+ T cells in the peripheral blood and lymphoid tissues. Viral entry into CD4+ cells is mediated by the interaction with a cellular chemokine receptor, the most common of which are CCR5 and CXCR4. Because subsequent viral replication requires cellular gene expression processes, activated CD4+ cells are the primary targets of productive HIV infection.[65] Recently scientists have been investigating an alternative approach to treating HIV-1/AIDS, based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (HIV-1-resistant) hematopoietic stem and progenitor cells (GM-HSPC).[66]

On 23 January 2009, the US Food and Drug Administration gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem-cell-based therapy on humans. The trial aimed evaluate the drug GRNOPC1, embryonic stem cell-derived oligodendrocyte progenitor cells, on patients with acute spinal cord injury. The trial was discontinued in November 2011 so that the company could focus on therapies in the "current environment of capital scarcity and uncertain economic conditions".[67] In 2013 biotechnology and regenerative medicine company BioTime (NYSEMKT:BTX) acquired Geron's stem cell assets in a stock transaction, with the aim of restarting the clinical trial.[68]

Scientists have reported that MSCs when transfused immediately within few hours post thawing may show reduced function or show decreased efficacy in treating diseases as compared to those MSCs which are in log phase of cell growth(fresh), so cryopreserved MSCs should be brought back into log phase of cell growth in invitro culture before these are administered for clinical trials or experimental therapies, re-culturing of MSCs will help in recovering from the shock the cells get during freezing and thawing. Various clinical trials on MSCs have failed which used cryopreserved product immediately post thaw as compared to those clinical trials which used fresh MSCs.[69]

Research currently conducted on horses, dogs, and cats can benefit the development of stem cell treatments in veterinary medicine and can target a wide range of injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis, osteochondrosis and muscular dystrophy both in large animals, as well as humans.[70][71][72][73] While investigation of cell-based therapeutics generally reflects human medical needs, the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach.[74] Companion animals can serve as clinically relevant models that closely mimic human disease.[75][76]

There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections.[110] There is other stem cell research that does not involve the destruction of a human embryo, and such research involves adult stem cells, amniotic stem cells, and induced pluripotent stem cells.

Stem-cell research and treatment was practiced in the People's Republic of China. The Ministry of Health of the People's Republic of China has permitted the use of stem-cell therapy for conditions beyond those approved of in Western countries. The Western World has scrutinized China for its failed attempts to meet international documentation standards of these trials and procedures.[111]

Since 2008 many universities, centers and doctors tried a diversity of methods; in Lebanon proliferation for stem cell therapy, in-vivo and in-vitro techniques were used, Thus this country is considered the launching place of the Regentime[112] procedure. The regenerative medicine also took place in Jordan and Egypt.[citation needed]

Stem-cell treatment is currently being practiced at a clinical level in Mexico. An International Health Department Permit (COFEPRIS) is required. Authorized centers are found in Tijuana, Guadalajara and Cancun. Currently undergoing the approval process is Los Cabos. This permit allows the use of stem cell.[citation needed]

In 2005, South Korean scientists claimed to have generated stem cells that were tailored to match the recipient. Each of the 11 new stem cell lines was developed using somatic cell nuclear transfer (SCNT) technology. The resultant cells were thought to match the genetic material of the recipient, thus suggesting minimal to no cell rejection.[113]

As of 2013, Thailand still considers Hematopoietic stem cell transplants as experimental. Kampon Sriwatanakul began with a clinical trial in October 2013 with 20 patients. 10 are going to receive stem-cell therapy for Type-2 diabetes and the other 10 will receive stem-cell therapy for emphysema. Chotinantakul's research is on Hematopoietic cells and their role for the hematopoietic system function in homeostasis and immune response.[114]

Today, Ukraine is permitted to perform clinical trials of stem-cell treatments (Order of the MH of Ukraine 630 "About carrying out clinical trials of stem cells", 2008) for the treatment of these pathologies: pancreatic necrosis, cirrhosis, hepatitis, burn disease, diabetes, multiple sclerosis, critical lower limb ischemia. The first medical institution granted the right to conduct clinical trials became the "Institute of Cell Therapy"(Kiev).

Other countries where doctors did stem cells research, trials, manipulation, storage, therapy: Brazil, Cyprus, Germany, Italy, Israel, Japan, Pakistan, Philippines, Russia, Switzerland, Turkey, United Kingdom, India, and many others.

Original post:
Stem-cell therapy - Wikipedia

Stem cell – Wikipedia

Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells. They are found in multicellular organisms. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cellsectoderm, endoderm and mesoderm (see induced pluripotent stem cells)but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.

There are three known accessible sources of autologous adult stem cells in humans:

Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures.

Adult stem cells are frequently used in various medical therapies (e.g., bone marrow transplantation). Stem cells can now be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through somatic cell nuclear transfer or dedifferentiation have also been proposed as promising candidates for future therapies.[1] Research into stem cells grew out of findings by Ernest A. McCulloch and James E. Till at the University of Toronto in the 1960s.[2][3]

The classical definition of a stem cell requires that it possess two properties:

Two mechanisms exist to ensure that a stem cell population is maintained:

Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[4]

In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone marrow or hematopoietic stem cells (HSCs) is the ability to transplant the cells and save an individual without HSCs. This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.

Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, in which single cells are assessed for their ability to differentiate and self-renew.[7][8] Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells shall behave in a similar manner in vivo. There is considerable debate as to whether some proposed adult cell populations are truly stem cells.[citation needed]

Embryonic stem (ES) cells are the cells of the inner cell mass of a blastocyst, an early-stage embryo.[9] Human embryos reach the blastocyst stage 45 days post fertilization, at which time they consist of 50150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.

During embryonic development these inner cell mass cells continuously divide and become more specialized. For example, a portion of the ectoderm in the dorsal part of the embryo specializes as 'neurectoderm', which will become the future central nervous system.[10] Later in development, neurulation causes the neurectoderm to form the neural tube. At the neural tube stage, the anterior portion undergoes encephalization to generate or 'pattern' the basic form of the brain. At this stage of development, the principal cell type of the CNS is considered a neural stem cell. These neural stem cells are pluripotent, as they can generate a large diversity of many different neuron types, each with unique gene expression, morphological, and functional characteristics. The process of generating neurons from stem cells is called neurogenesis. One prominent example of a neural stem cell is the radial glial cell, so named because it has a distinctive bipolar morphology with highly elongated processes spanning the thickness of the neural tube wall, and because historically it shared some glial characteristics, most notably the expression of glial fibrillary acidic protein (GFAP).[11][12] The radial glial cell is the primary neural stem cell of the developing vertebrate CNS, and its cell body resides in the ventricular zone, adjacent to the developing ventricular system. Neural stem cells are committed to the neuronal lineages (neurons, astrocytes, and oligodendrocytes), and thus their potency is restricted.[10]

Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES) derived from the early inner cell mass. Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin as an extracellular matrix (for support) and require the presence of leukemia inhibitory factor (LIF). Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic fibroblast growth factor (bFGF or FGF-2).[13] Without optimal culture conditions or genetic manipulation,[14] embryonic stem cells will rapidly differentiate.

A human embryonic stem cell is also defined by the expression of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[15] The cell surface antigens most commonly used to identify hES cells are the glycolipids stage specific embryonic antigen 3 and 4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. By using human embryonic stem cells to produce specialized cells like nerve cells or heart cells in the lab, scientists can gain access to adult human cells without taking tissue from patients. They can then study these specialized adult cells in detail to try and catch complications of diseases, or to study cells reactions to potentially new drugs. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[16]

There are currently no approved treatments using embryonic stem cells. The first human trial was approved by the US Food and Drug Administration in January 2009.[17] However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal cord injury research. On November 14, 2011 the company conducting the trial (Geron Corporation) announced that it will discontinue further development of its stem cell programs.[18] ES cells, being pluripotent cells, require specific signals for correct differentiationif injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[19] Due to ethical considerations, many nations currently have moratoria or limitations on either human ES cell research or the production of new human ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.

Human embryonic stem cell colony on mouse embryonic fibroblast feeder layer

The primitive stem cells located in the organs of fetuses are referred to as fetal stem cells.[20] There are two types of fetal stem cells:

Adult stem cells, also called somatic (from Greek , "of the body") stem cells, are stem cells which maintain and repair the tissue in which they are found.[22] They can be found in children, as well as adults.[23]

Pluripotent adult stem cells are rare and generally small in number, but they can be found in umbilical cord blood and other tissues.[24] Bone marrow is a rich source of adult stem cells,[25] which have been used in treating several conditions including liver cirrhosis,[26] chronic limb ischemia [27] and endstage heart failure.[28] The quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years.[29] Much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities.[30] DNA damage accumulates with age in both stem cells and the cells that comprise the stem cell environment. This accumulation is considered to be responsible, at least in part, for increasing stem cell dysfunction with aging (see DNA damage theory of aging).[31]

Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, dental pulp stem cell, etc.).[32][33]

Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants.[34] Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.[35]

The use of adult stem cells in research and therapy is not as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, in instances where adult stem cells are obtained from the intended recipient (an autograft), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research.[36]

Multipotent stem cells are also found in amniotic fluid. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.[37] Amniotic stem cells are a topic of active research.

Use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of cells. Roman Catholic teaching forbids the use of embryonic stem cells in experimentation; accordingly, the Vatican newspaper "Osservatore Romano" called amniotic stem cells "the future of medicine".[38]

It is possible to collect amniotic stem cells for donors or for autologuous use: the first US amniotic stem cells bank [39][40] was opened in 2009 in Medford, MA, by Biocell Center Corporation[41][42][43] and collaborates with various hospitals and universities all over the world.[44]

These are not adult stem cells, but rather adult cells (e.g. epithelial cells) reprogrammed to give rise to pluripotent capabilities. Using genetic reprogramming with protein transcription factors, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue.[45][46][47]Shinya Yamanaka and his colleagues at Kyoto University used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4[45] in their experiments on human facial skin cells. Junying Yu, James Thomson, and their colleagues at the University of WisconsinMadison used a different set of factors, Oct4, Sox2, Nanog and Lin28,[45] and carried out their experiments using cells from human foreskin.

As a result of the success of these experiments, Ian Wilmut, who helped create the first cloned animal Dolly the Sheep, has announced that he will abandon somatic cell nuclear transfer as an avenue of research.[48]

Frozen blood samples can be used as a source of induced pluripotent stem cells, opening a new avenue for obtaining the valued cells.[49]

To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[50]

An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals decapentaplegic and adherens junctions that prevent germarium stem cells from differentiating.[51][52]

Stem cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is a form of stem cell therapy that has been used for many years without controversy. No stem cell therapies other than bone marrow transplant are widely used.[53][54]

Stem cell treatments may require immunosuppression because of a requirement for radiation before the transplant to remove the person's previous cells, or because the patient's immune system may target the stem cells. One approach to avoid the second possibility is to use stem cells from the same patient who is being treated.

Pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. It is also difficult to obtain the exact cell type needed, because not all cells in a population differentiate uniformly. Undifferentiated cells can create tissues other than desired types.[55]

Some stem cells form tumors after transplantation;[56] pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors despite multipotency.[citation needed]

Some of the fundamental patents covering human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation (WARF) they are patents 5,843,780, 6,200,806, and 7,029,913 invented by James A. Thomson. WARF does not enforce these patents against academic scientists, but does enforce them against companies.[57]

In 2006, a request for the US Patent and Trademark Office (USPTO) to re-examine the three patents was filed by the Public Patent Foundation on behalf of its client, the non-profit patent-watchdog group Consumer Watchdog (formerly the Foundation for Taxpayer and Consumer Rights).[57] In the re-examination process, which involves several rounds of discussion between the USTPO and the parties, the USPTO initially agreed with Consumer Watchdog and rejected all the claims in all three patents,[58] however in response, WARF amended the claims of all three patents to make them more narrow, and in 2008 the USPTO found the amended claims in all three patents to be patentable. The decision on one of the patents (7,029,913) was appealable, while the decisions on the other two were not.[59][60] Consumer Watchdog appealed the granting of the '913 patent to the USTPO's Board of Patent Appeals and Interferences (BPAI) which granted the appeal, and in 2010 the BPAI decided that the amended claims of the '913 patent were not patentable.[61] However, WARF was able to re-open prosecution of the case and did so, amending the claims of the '913 patent again to make them more narrow, and in January 2013 the amended claims were allowed.[62]

In July 2013, Consumer Watchdog announced that it would appeal the decision to allow the claims of the '913 patent to the US Court of Appeals for the Federal Circuit (CAFC), the federal appeals court that hears patent cases.[63] At a hearing in December 2013, the CAFC raised the question of whether Consumer Watchdog had legal standing to appeal; the case could not proceed until that issue was resolved.[64]

Diseases and conditions where stem cell treatment is being investigated include:

Research is underway to develop various sources for stem cells, and to apply stem cell treatments for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions.[80]

In more recent years, with the ability of scientists to isolate and culture embryonic stem cells, and with scientists' growing ability to create stem cells using somatic cell nuclear transfer and techniques to create induced pluripotent stem cells, controversy has crept in, both related to abortion politics and to human cloning.

Hepatotoxicity and drug-induced liver injury account for a substantial number of failures of new drugs in development and market withdrawal, highlighting the need for screening assays such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process.[81]

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Stem cell - Wikipedia

CCR5 – Wikipedia

CCR5 Identifiers Aliases CCR5, CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5, CMKBR5, IDDM22, C-C motif chemokine receptor 5 (gene/pseudogene) External IDs OMIM: 601373 MGI: 107182 HomoloGene: 37325 GeneCards: CCR5 Targeted by Drug aplaviroc, cenicriviroc, maraviroc, vicriviroc[1] Orthologs Species Human Mouse Entrez Ensembl UniProt RefSeq (mRNA) RefSeq (protein) Location (UCSC) Chr 3: 46.37 46.38 Mb Chr 9: 124.12 124.15 Mb PubMed search [2] [3] Wikidata View/Edit Human View/Edit Mouse

C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. This is the process by which T cells are attracted to specific tissue and organ targets. Many forms of HIV, the virus that causes AIDS, initially use CCR5 to enter and infect host cells. Certain individuals carry a mutation known as CCR5-32 in the CCR5 gene, protecting them against these strains of HIV.

In humans, the CCR5 gene that encodes the CCR5 protein is located on the short (p) arm at position 21 on chromosome 3. Certain populations have inherited the Delta 32 mutation resulting in the genetic deletion of a portion of the CCR5 gene. Homozygous carriers of this mutation are resistant to M-tropic strains of HIV-1 infection.[4][5][6][7][8][9]

The CCR5 protein belongs to the beta chemokine receptors family of integral membrane proteins.[10][11] It is a G proteincoupled receptor[10] which functions as a chemokine receptor in the CC chemokine group.

CCR5's cognate ligands include CCL3, CCL4 (also known as MIP 1 and 1, respectively), and CCL3L1.[12][13] CCR5 furthermore interacts with CCL5 (a chemotactic cytokine protein also known as RANTES).[12][14][15]

CCR5 is predominantly expressed on T cells, macrophages, dendritic cells, eosinophils and microglia. It is likely that CCR5 plays a role in inflammatory responses to infection, though its exact role in normal immune function is unclear. Regions of this protein are also crucial for chemokine ligand binding, functional response of the receptor, and HIV co-receptor activity.[16]

HIV-1 most commonly uses the chemokine receptors CCR5 and/or CXCR4 as co-receptors to enter target immunological cells.[17] These receptors are located on the surface of host immune cells whereby they provide a method of entry for the HIV-1 virus to infect the cell.[18] The HIV-1 envelope glycoprotein structure is essential in enabling the viral entry of HIV-1 into a target host cell.[18] The envelope glycoprotein structure consists of two protein subunits cleaved from a Gp160 protein precursor encoded for by the HIV-1 env gene: the Gp120 external subunit, and the Gp41 transmembrane subunit.[18] This envelope glycoprotein structure is arranged into a spike-like structure located on the surface of the virion and consists of a trimer of three Gp120-Gp41 hetero-dimers.[18] The Gp120 envelope protein is a chemokine mimic.[17] It lacks the unique structure of a chemokine, however it is still capable of binding to the CCR5 and CXCR4 chemokine receptors.[17] During HIV-1 infection, the Gp120 envelope glycoprotein subunit binds to a CD4 glycoprotein and a HIV-1 co-receptor expressed on a target cell- forming a heterotrimeric complex.[17] The formation of this complex stimulates the release of a fusogenic peptide inducing the fusion of the viral membrane with the membrane of the target host cell.[17] Because binding to CD4 alone can sometimes result in gp120 shedding, gp120 must next bind to co-receptor CCR5 in order for fusion to proceed. The tyrosine sulfated amino terminus of this co-receptor is the "essential determinant" of binding to the gp120 glycoprotein.[19] Co-receptor recognition also include the V1-V2 region of gp120, and the bridging sheet (an antiparallel, 4-stranded sheet that connects the inner and outer domains of gp120). The V1-V2 stem can influence "co-receptor usage through its peptide composition as well as by the degree of N-linked glycosylation." Unlike V1-V2 however, the V3 loop is highly variable and thus is the most important determinant of co-receptor specificity.[19] The normal ligands for this receptor, RANTES, MIP-1, and MIP-1, are able to suppress HIV-1 infection in vitro. In individuals infected with HIV, CCR5-using viruses are the predominant species isolated during the early stages of viral infection,[20] suggesting that these viruses may have a selective advantage during transmission or the acute phase of disease. Moreover, at least half of all infected individuals harbor only CCR5-using viruses throughout the course of infection.

CCR5 is the primary co-receptor used by gp120 sequentially with CD4. This bind results in gp41, the other protein product of gp160, to be released from its metastable conformation and insert itself into the membrane of the host cell. Although it hasn't been finalized as a proven theory yet, binding of gp120-CCR5 involves two crucial steps: 1) The tyrosine sulfated amino terminus of this co-receptor is an "essential determinant" of binding to gp120 (as stated previously) 2) Following step 1., there must be reciprocal action (synergy, intercommunication) between gp120 and the CCR5 transmembrane domains [19]

CCR5 is essential for the spread of the R5-strain of the HIV-1 virus.[21] Knowledge of the mechanism by which this strain of HIV-1 mediates infection has prompted research into the development of therapeutic interventions to block CCR5 function.[22] A number of new experimental HIV drugs, called CCR5 receptor antagonists, have been designed to interfere with the associative binding between the Gp120 envelope protein and the HIV co-receptor CCR5.[21] These experimental drugs include PRO140 (CytoDyn), Vicriviroc (Phase III trials were cancelled in July 2010) (Schering Plough), Aplaviroc (GW-873140) (GlaxoSmithKline) and Maraviroc (UK-427857) (Pfizer). Maraviroc was approved for use by the FDA in August 2007.[21] It is the only one thus far approved by the FDA for clinical use, thus becoming the first CCR5 inhibitor.[19] A problem of this approach is that, while CCR5 is the major co-receptor by which HIV infects cells, it is not the only such co-receptor. It is possible that under selective pressure HIV will evolve to use another co-receptor. However, examination of viral resistance to AD101, molecular antagonist of CCR5, indicated that resistant viruses did not switch to another coreceptor (CXCR4) but persisted in using CCR5, either through binding to alternative domains of CCR5, or by binding to the receptor at a higher affinity. However, because there is still another co-receptor available, this indicates that lacking the CCR5 gene doesn't make one immune to the virus; it simply implies that it would be more challenging for the individual to contract it. Also, the virus still has access to the CD4. Unlike CCR5, which the body apparently doesn't really need due to those still living healthy lives even with the lack of/or absence of the gene (as a result of the delta 32 mutation), CD4 is critical in the bodies defense system (fighting against infection).[23] Even without the availability of either co-receptors (even CCR5), the virus can still invade cells if gp41 were to go through an alteration (including its cytoplasmic tail), resulting in the independence of CD4 without the need of CCR5 and/or CXCR4 as a doorway.[24]

CCR5-32 (or CCR5-D32 or CCR5 delta 32) is an allele of CCR5.[25][26]

CCR5 32 is a 32-base-pair deletion that introduces a premature stop codon into the CCR5 receptor locus, resulting in a nonfunctional receptor.[27][28] CCR5 is required for M-tropic HIV-1 virus entry.[29] Individuals homozygous for CCR5 32 do not express functional CCR5 receptors on their cell surfaces and are resistant to HIV-1 infection, despite multiple high-risk exposures.[29] Individuals heterozygous for the mutant allele have a greater than 50% reduction in functional CCR5 receptors on their cell surfaces due to dimerization between mutant and wild-type receptors that interferes with transport of CCR5 to the cell surface.[30] Heterozygote carriers are resistant to HIV-1 infection relative to wild types and when infected, heterozygotes exhibit reduced viral loads and a 2-3-year-slower progression to AIDS relative to wild types.[27][29][31] Heterozygosity for this mutant allele also has shown to improve one's virological response to anti-retroviral treatment.[32] CCR5 32 has an (heterozygote) allele frequency of 10% in Europe, and a homozygote frequency of 1%.

The CCR5 32 allele is notable for its recent origin, unexpectedly high frequency, and distinct geographic distribution,[33] which together suggest that (a) it arose from a single mutation, and (b) it was historically subject to positive selection.

Two studies have used linkage analysis to estimate the age of the CCR5 32 deletion, assuming that the amount of recombination and mutation observed on genomic regions surrounding the CCR5 32 deletion would be proportional to the age of the deletion.[26][34] Using a sample of 4000 individuals from 38 ethnic populations, Stephens et al. estimated that the CCR5-32 deletion occurred 700 years ago (275-1875, 95% confidence interval). Another group, Libert et al. (1998), estimated the age of the CCR5 32 mutation is based on the microsatellite mutations to be 2100 years (700-4800, 95% confidence interval). On the basis of observed recombination events, they estimated the age of the mutation to be 2250 years (900-4700, 95% confidence interval).[34] A third hypothesis relies on the on the north-to-south gradient of allele frequency in Europe which shows that the highest allele frequency occurred in Nordic regions such as Iceland, Norway and Sweden and lowest allele frequency in the south. Because the Vikings historically occupied these countries, it may be possible that the allele spread throughout Europe was due to the Viking dispersal in the 8th to 10th century.[35] Vikings were later replaced by the Varangians in Russia, which migrated East which may have contributed to the observed east-to-west cline of allele frequency.[33][35]

HIV-1 was initially transmitted from chimpanzees (Pan troglodytes) to humans in the early 1900s in Southeast Cameroon, Africa,[36] through exposure to infected blood and body fluids while butchering bushmeat.[37] However, HIV-1 was effectively absent from Europe until the late 1980s.[38] Therefore, given the average age of roughly 1000 years for the CCR5-32 allele, it can be established that HIV-1 did not exert selection pressure on the human population for long enough to achieve the current frequencies.[33] Hence, other pathogens have been suggested agents of positive selection for CCR5 32. The first major one being bubonic plague (Yersinia pestis), and later, smallpox (Variola major). Other data suggest that the allele frequency resulted as a negative selection pressure as a result of pathogens that became more widespread during Roman expansion.[39] The idea that negative selection played a role in its low frequency is also supported by experiments using knockout mice and Influenza A, which demonstrated that the presence of the CCR5 receptor is important for efficient response to a pathogen.[40][41]

Several lines of evidence suggest that the CCR5 32 allele evolved only once.[33] First, CCR5 32 has a relatively high frequency in several different Caucasian populations but is comparatively absent in Asian, Middle Eastern and American Indian populations,[26] suggesting that a single mutation occurred after divergence of Caucasians from their African ancestor).[26][27][42] Second, genetic linkage analysis indicates that the mutation occurs on a homogenous genetic background, implying that inheritance of the mutation occurred from a common ancestor.[34] This was demonstrated by showing that the CCR5 32 allele is in strong linkage disequilibrium with highly polymorphic microsatellites. More than 95% of CCR5 32 chromosomes also carried the IRI3.1-0 allele, while 88% carried the IRI3.2 allele. By contrast, the microsatellite markers IRI3.1-0 and IRI3.2-0 were found in only 2 or 1.5% of chromosomes carrying a wild-type CCR5 allele.[34] This evidence of linkage disequilibrium supports the hypothesis that most, if not all, CCR5 32 alleles arose from a single mutational event. Finally, the CCR5 32 allele has a unique geographical distribution indicating a single Northern origin followed by migration. A study measuring allele frequencies in 18 European populations found a North-to-South gradient, with the highest allele frequencies in Finnish and Mordvinian populations (16%), and the lowest in Sardinia (4%).[34]

In the absence of selection, a single mutation would take an estimated 127,500 years to rise to a population frequency of 10%.[26] Estimates based on genetic recombination and mutation rates place the age of the allele between 1000 and 2000 years. This discrepancy is a signature of positive selection.

It is estimated that HIV-1 entered the human population in Africa in the early 1900s,[36] symptomatic infections were not reported until the 1980s. The HIV-1 epidemic is therefore far too young to be the source of positive selection that drove the frequency of CCR5 32 from zero to 10% in 2000 years. In 1998, Stephens et al. suggested that bubonic plague (Yersinia pestis) had exerted positive selective pressure on CCR5 32.[26] This hypothesis was based on the timing and severity of the Black Death pandemic, which killed 30% of the European population of all ages between 1346 and 1352.[43] After the Black Death, there were less severe, intermittent, epidemics. Individual cities experienced high mortality, but overall mortality in Europe was only a few percent.[43][44][45] In 1655-1656 a second pandemic called the "Great Plague" killed 15-20% of Europes population.[43][46] Importantly, the plague epidemics were intermittent. Bubonic plague is a zoonotic disease, primarily infecting rodents and spread by fleas and only occasionally infecting humans.[47] Human-to-human infection of bubonic plague does not occur, though it can occur in pneumonic plague, which infects the lungs.[48] Only when the density of rodents is low are infected fleas forced to feed on alternative hosts such as humans, and under these circumstances a human epidemic may occur.[47] Based on population genetic models, Galvani and Slatkin (2003) argue that the intermittent nature of plague epidemics did not generate a sufficiently strong selective force to drive the allele frequency of CCR5 32 to 10% in Europe.[25]

To test this hypothesis, Galvani and Slatkin (2003) modeled the historical selection pressures produced by plague and smallpox.[25] Plague was modeled according to historical accounts,[49][50] while age-specific smallpox mortality was gleaned from the age distribution of smallpox burials in York (England) between 1770 and 1812.[44] Smallpox preferentially infects young, pre-reproductive members of the population since they are the only individuals who are not immunized or dead from past infection. Because smallpox preferentially kills pre-reproductive members of a population, it generates stronger selective pressure than plague.[25] Unlike plague, smallpox does not have an animal reservoir and is only transmitted from human to human.[51][52] The authors calculated that if plague were selecting for CCR5 32, the frequency of the allele would still be less than 1%, while smallpox has exerted a selective force sufficient to reach 10%.

The hypothesis that smallpox exerted positive selection for CCR5 32 is also biologically plausible, since poxviruses, like HIV, are viruses that enter white blood cells by using chemokine receptors.[53] By contrast, Yersinia pestis is a bacterium with a very different biology.

Although Caucasians are the only population with a high frequency of CCR5 32, they are not the only population that has been subject to selection by smallpox, which had a worldwide distribution before it was declared eradicated in 1980. The earliest unmistakable descriptions of smallpox appear in the 5th century A.D. in China, the 7th century A.D. in India and the Mediterranean, and the 10th century A.D. in southwestern Asia.[52] By contrast, the CCR5 32 mutation is found only in European, West Asian, and North African populations.[54] The anomalously high frequency of CCR5 32 in these populations appears to require both a unique origin in Northern Europe and subsequent selection by smallpox.

Research has not yet revealed a cost of carrying the CCR5 null mutation that is as dramatic as the benefit conferred in the context of HIV-1 exposure. In general, research suggests that the CCR5 32 mutation protects against diseases caused by certain pathogens but may also play a deleterious role in postinfection inflammatory processes, which can injure tissue and create further pathology.[55] The best evidence for this proposed antagonistic pleiotropy is found in flavivirus infections. In general many viral infections are asymptomatic or produce only mild symptoms in the vast majority of the population. However, certain unlucky individuals experience a particularly destructive clinical course, which is otherwise unexplained but appears to be genetically mediated. Patients homozygous for CCR5 32 were found to be at higher risk for a neuroinvasive form of tick-borne encephalitis (a flavivirus).[56] In addition, functional CCR5 may be required to prevent symptomatic disease after infection with West Nile virus, another flavivirus; CCR5 32 was associated with early symptom development and more pronounced clinical manifestations after infection with West Nile virus.[57]

This finding in humans confirmed a previously-observed experiment in an animal model of CCR5 32 homozygosity. After infection with West Nile Virus, CCR5 32 mice had markedly increased viral titers in the central nervous system and had increased mortality[58] compared with that of wild-type mice, thus suggesting that CCR5 expression was necessary to mount a strong host defense against West Nile virus.

CCR5 32 can be beneficial to the host in some infections (e.g., HIV-1, possibly smallpox), but detrimental in others (e.g., tick-borne encephalitis, West Nile virus). Whether CCR5 function is helpful or harmful in the context of a given infection depends on a complex interplay between the immune system and the pathogen.

A genetic approach involving intrabodies that block CCR5 expression has been proposed as a treatment for HIV-1 infected individuals.[59] When T-cells modified so they no longer express CCR5 were mixed with unmodified T-cells expressing CCR5 and then challenged by infection with HIV-1, the modified T-cells that do not express CCR5 eventually take over the culture, as HIV-1 kills the non-modified T-cells. This same method might be used in vivo to establish a virus resistant cell pool in infected individuals.[59]

This hypothesis was tested in an AIDS patient who had also developed myeloid leukemia, and was treated with chemotherapy to suppress the cancer. A bone marrow transplant containing stem cells from a matched donor was then used to restore the immune system. However, the transplant was performed from a donor with 2 copies of CCR5-32 mutation gene. After 600 days, the patient was healthy and had undetectable levels of HIV in the blood and in examined brain and rectal tissues.[5][60] Before the transplant, low levels of HIV X4, which does not use the CCR5 receptor, were also detected. Following the transplant, however, this type of HIV was not detected either, further baffling doctors.[5] However, this is consistent with the observation that cells expressing the CCR5-32 variant protein lack both the CCR5 and CXCR4 receptors on their surfaces, thereby conferring resistance to a broad range of HIV variants including HIV X4.[61] After over six years, the patient has maintained the resistance to HIV and has been pronounced cured of the HIV infection.[6]

Enrollment of HIV-positive patients in a clinical trial was started in 2009 in which the patients' cells were genetically modified with a zinc finger nuclease to carry the CCR5-32 trait and then reintroduced into the body as a potential HIV treatment.[62][63] Results reported in 2014 were promising.[9]

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JCI – Welcome

BACKGROUND. Low vitamin D status in pregnancy was proposed as a risk factor of preeclampsia.

METHODS. We assessed the effect of vitamin D supplementation (4,400 vs. 400 IU/day), initiated early in pregnancy (1018 weeks), on the development of preeclampsia. The effects of serum vitamin D (25-hydroxyvitamin D [25OHD]) levels on preeclampsia incidence at trial entry and in the third trimester (3238 weeks) were studied. We also conducted a nested case-control study of 157 women to investigate peripheral blood vitamin Dassociated gene expression profiles at 10 to 18 weeks in 47 participants who developed preeclampsia.

RESULTS. Of 881 women randomized, outcome data were available for 816, with 67 (8.2%) developing preeclampsia. There was no significant difference between treatment (N = 408) or control (N = 408) groups in the incidence of preeclampsia (8.08% vs. 8.33%, respectively; relative risk: 0.97; 95% CI, 0.611.53). However, in a cohort analysis and after adjustment for confounders, a significant effect of sufficient vitamin D status (25OHD 30 ng/ml) was observed in both early and late pregnancy compared with insufficient levels (25OHD

CONCLUSIONS. Vitamin D supplementation initiated in weeks 1018 of pregnancy did not reduce preeclampsia incidence in the intention-to-treat paradigm. However, vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeclampsia. Differentially expressed vitamin Dassociated transcriptomes implicated the emergence of an early pregnancy, distinctive immune response in women who went on to develop preeclampsia.


FUNDING. Quebec Breast Cancer Foundation and Genome Canada Innovation Network. This trial was funded by the National Heart, Lung, and Blood Institute. For details see Acknowledgments.

Hooman Mirzakhani, Augusto A. Litonjua, Thomas F. McElrath, George OConnor, Aviva Lee-Parritz, Ronald Iverson, George Macones, Robert C. Strunk, Leonard B. Bacharier, Robert Zeiger, Bruce W. Hollis, Diane E. Handy, Amitabh Sharma, Nancy Laranjo, Vincent Carey, Weilliang Qiu, Marc Santolini, Shikang Liu, Divya Chhabra, Daniel A. Enquobahrie, Michelle A. Williams, Joseph Loscalzo, Scott T. Weiss

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8 – OMICS International Conference

Conference Series invites all the participants from all over the world to attend"8th European Immunology Conference, June 29-July 01, 2017 Madrid, Spain, includesprompt keynote presentations, Oral talks, Poster presentations and Exhibitions.

European ImmunologyConferenceis to gathering people in academia and society interested inimmunologyto share the latest trends and important issues relevant to our field/subject area.Immunology Conferencesbrings together the global leaders in Immunology and relevant fields to present their research at this exclusive scientific program. TheImmunology Conferencehosting presentations from editors of prominent refereed journals, renowned and active investigators and decision makers in the field of Immunology.European Immunology ConferenceOrganizing Committee also invites Young investigators at every career stage to submit abstracts reporting their latest scientific findings in oral and poster sessions.

Track:1Cellular Immunology

The study of the molecular and cellular components that comprise the immune system, including their function and interaction, is the central science ofimmunology. The immune system has been divided into a more primitive innate immune system and, in vertebrates, an acquired oradaptive immune system

The field concerning the interactions among cells and molecules of the immunesystem,and how such interactions contribute to the recognition and elimination of pathogens. Humans possess a range of non-specific mechanical and biochemical defences against routinely encountered bacteria, parasites, viruses, and fungi. The skin, for example, is an effective physical barrier to infection. Basic chemical defences are also present in blood, saliva, and tears, and on mucous membranes. True protection stems from the host's ability to mount responses targeted to specific organisms, and to retain a form of memory that results in a rapid, efficient response to a given organism upon a repeat encounter. This more formal sense of immunity, termed adaptive immunity, depends upon the coordinated activities of cells and molecules of the immune system.

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Track: 2Inflammatory/Autoimmune Diseases

Autoimmune diseasescan affect almost any part of the body, including the heart, brain, nerves, muscles, skin, eyes, joints, lungs, kidneys, glands, the digestive tract, and blood vessels.

The classic sign of an autoimmune disease is inflammation, which can cause redness, heat, pain, and swelling. How an autoimmune disease affects you depends on what part of the body is targeted. If the disease affects the joints, as inrheumatoid arthritis, you might have joint pain, stiffness, and loss of function. If it affects the thyroid, as in Graves disease and thyroiditis, it might cause tiredness, weight gain, and muscle aches. If it attacks the skin, as it does in scleroderma/systemic sclerosis, vitiligo, andsystemic lupus erythematosus(SLE), it can cause rashes, blisters, and colour changes. Many autoimmune diseases dont restrict themselves to one part of the body. For example, SLE can affect the skin, joints, kidneys, heart, nerves, blood vessels, and more. Type 1 diabetes can affect your glands, eyes, kidneys, muscles, and more.

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Track: 3T-Cells and B-Cells

T cell: A type of white blood cell that is of key importance to the immune system and is at the core of adaptive immunity, the system that tailors the body's immune response to specific pathogens. The T cells are like soldiers who search out and destroy the targeted invaders. Immature T cells (termed T-stem cells) migrate to the thymus gland in the neck, where they mature and differentiate into various types of mature T cells and become active in the immune system in response to a hormone called thymosin and other factors. T-cells that are potentially activated against the body's own tissues are normally killed or changed ("down-regulated") during this maturational process.There are several different types of mature T cells. Not all of their functions are known. T cells can produce substances called cytokines such as the interleukins which further stimulate the immune response. T-cell activation is measured as a way to assess the health of patients withHIV/AIDSand less frequently in other disorders. T cell are also known as T lymphocytes. The "T" stands for "thymus" -- the organ in which these cells mature. As opposed to B cells which mature in the bone marrow.B cells, also known asBlymphocytes, are a type of white bloodcellof the lymphocyte subtype. They function in thehumoral immunitycomponent of the adaptive immune system by secreting antibodies. Many B cells mature into what are called plasma cells that produce antibodies (proteins) necessary to fight off infections while other B cells mature into memory B cells. All of the plasma cells descended from a single B cell produce the same antibody which is directed against the antigen that stimulated it to mature. The same principle holds with memory B cells. Thus, all of the plasma cells and memory cells "remember" the stimulus that led to their formation. The maturation of B cells takes place in birds in an organ called the bursa of Fabricus. B cells in mammals mature largely in the bone marrow. The B cell, or B lymphocyte, is thus an immunologically important cell. It is not thymus-dependent, has a short lifespan, and is responsible for the production ofimmunoglobulins.It expresses immunoglobulins on its surface.

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Track: 4Cancer and Tumor Immunobiology

The tumour is an important aspect of cancer biology that contributes to tumour initiation, tumour progression and responses to therapy. Cells and molecules of the immune system are a fundamental component of the tumour microenvironment. Importantly,therapeutic strategies for cancer treatmentcan harness the immune system to specifically target tumour cells and this is particularly appealing owing to the possibility of inducing tumour-specific immunological memory, which might cause long-lasting regression and prevent relapse in cancer patients.The composition and characteristics of the tumour microenvironment vary widely and are important in determining the anti-tumour immune response.Immunotherapyis a new class ofcancer treatmentthat works to harness the innate powers of the immune system to fight cancer. Because of the immune system's unique properties, these therapies may hold greater potential than current treatment approaches to fight cancer more powerfully, to offer longer-term protection against the disease, to come with fewer side effects, and to benefit more patients with more cancer

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Track: 5 Vaccines

A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters. There are two basictypes of vaccines: live attenuated and inactivated. The characteristics of live and inactivatedvaccinesare different, and these characteristics determine how thevaccineis used. Liveattenuatedvaccinesare produced by modifying a disease-producing (wild) virus or bacteria in a laboratory.

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Track: 6Immunotherapy

Immunotherapy,also called biologic therapy, is a type of cancer treatment designed to boost the body's natural defences to fight the cancer. It uses materials either made by the body or in a laboratory to improve, target, or restore immune system function. Immunotherapy is treatment that uses certain parts of a persons immune system to fight diseases such as cancer. This can be done in a couple of ways:1)Stimulating your own immune system to work harder or smarter to attack cancer cells2)Giving you immune system components, such as man-made immune system proteins. Some types of immunotherapy are also sometimes called biologic therapy or biotherapy.

In the last few decadesimmunotherapyhas become an important part of treating some types of cancer. Newer types of immune treatments are now being studied, and theyll impact how we treat cancer in the future. Immunotherapy includes treatments that work in different ways. Some boost the bodys immune system in a very general way. Others help train the immune system to attack cancer cells specifically. Immunotherapy works better for some types of cancer than for others. Its used by itself for some of these cancers, but for others it seems to work better when used with other types of treatment.

Many different types of immunotherapy are used to treat cancer. They include:Monoclonal antibodies,Adoptive cell transfer,Cytokines, Treatment Vaccines, BCG,

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Track: 7Neuro Immunology

Neuroimmunology, a branch of immunologythat deals especially with the inter relationships of the nervous system and immune responses andautoimmune disorders. It deals with particularly fundamental and appliedneurobiology,meetings onneurology,neuropathology, neurochemistry,neurovirology, neuroendocrinology, neuromuscular research,neuropharmacologyand psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays).

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Track: 8Infectious Diseases and Immune System

Infectious diseases are caused by pathogenic microorganisms, such as bacteria, viruses, parasites or fungi; the diseases can be spread, directly or indirectly, from one person to another.Zoonotic diseasesare infectious diseases of animals that can cause disease when transmitted to humans. Some infectious diseases can be passed from person to person. Some are transmitted by bites from insects or animals. And others are acquired by ingesting contaminated food or water or being exposed to organisms in the environment. Signs and symptoms vary depending on the organism causing the infection, but often include fever and fatigue. Mild complaints may respond to rest and home remedies, while some life-threatening infections may require hospitalization.

Many infectious diseases, such as measles andchickenpox, can be prevented by vaccines. Frequent and thorough hand-washing also helps protect you from infectious diseases

There are four main kinds of germs:

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Track: 9Reproductive Immunology,

Reproductive immunologyrefers to a field of medicine that studies interactions (or the absence of them) between the immune system and components related to thereproductivesystem, such as maternal immune tolerance towards the fetus, orimmunologicalinteractions across the blood-testis barrier. The immune system refers to all parts of the body that work to defend it against harmful enemies. In people with immunological fertility problems their body identifies part of reproductive function as an enemy and sendsNatural Killer (NK) cellsto attack. A healthy immune response would only identify an enemy correctly and attack only foreign invaders such as a virus, parasite, bacteria, ect.

The concept of reproductive immunology is not widely accepted by all physicians.Those patients who have had repeated miscarriages and multiple failed IVF's find themselves exploring it's possibilities as the reason. With an increased amount of success among treating any potential immunological factors, the idea of reproductive immunology can no longer be overlooked.The failure to conceive is often due to immunologic problems that can lead to very early rejection of the embryo, often before the pregnancy can be detected by even the most sensitive tests. Women can often produce perfectly healthy embryos that are lost through repeated "mini miscarriages." This most commonly occurs in women who have conditions such asendometriosis, an under-active thyroid gland or in cases of so called "unexplained infertility." It has been estimated that an immune factor may be involved in up to 20% of couples with otherwiseunexplained infertility. These are all conditions where abnormalities of the womans immune system may play an important role.

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Track:10Auto Immunity,

Autoimmunityis the system ofimmuneresponses of an organism against its own cells and tissues. Any disease that results from such an aberrantimmuneresponse is termed an autoimmune disease.

Autoimmunity is present to some extent in everyone and is usually harmless. However, autoimmunity can cause a broad range of human illnesses, known collectively as autoimmune diseases. Autoimmune diseases occur when there is progression from benign autoimmunity to pathogenicautoimmunity. This progression is determined by genetic influences as well as environmental triggers. Autoimmunity is evidenced by the presence of autoantibodies (antibodies directed against the person who produced them) and T cells that are reactive with host antigens.

Autoimmune disorders

An autoimmune disorder occurs whenthe bodys immune systemattacks and destroys healthy body tissue by mistake. There are more than 80 types of autoimmune disorders.


The white blood cells in the bodys immune system help protect against harmful substances. Examples include bacteria, viruses,toxins,cancercells, and blood and tissue from outside the body. These substances contain antigens. The immune system producesantibodiesagainst these antigens that enable it to destroy these harmful substances. When you have an autoimmune disorder, your immune system does not distinguish between healthy tissue and antigens. As a result, the body sets off a reaction that destroys normal tissues. The exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or viruses) or drugs may trigger changes that confuse the immune system. This may happen more often in people who have genes that make them more prone toautoimmune disorders.

An autoimmune disorder may result in:

A person may have more than one autoimmune disorder at the same time. Common autoimmune disorders include:

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9thworld congress & expo on Immunology, Oct 02-04, 2017, Toronto, Canada; 3rdAntibodies and Bio Therapeutics Congress, November 02-03, 2017 Las Vegas, USA; Molecular Immunology & Immunogenetics Congress, March 20-21, 2017 Rome, Italy; 3nd International Congress on Neuroimmunology and Therapeutics, September 18-19, 2017 Philadelphia, USA; 18th International Conference on Immunology (ICI) Dec 12-13, 2016, Bangkok, Thailand; Annual Meeting on Immunology and Immunologist, July 03-05, 2017 Malyasia, Kuala lumpur; British Society for Immunology Congress, Dec 06-09, 2016, Liverpool, United Kingdom; 7thInternational Conference on Allergy, Asthma and Clinical Immunology; Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology (C7), March 19 - 23, 2017, Whistler, British Columbia, Canada

Track: 11Costimmulatory pathways in multiple sclerosis

Costimulatory moleculescan be categorized based either on their functional attributes or on their structure. The costimulatory molecules discussed in this review will be divided into (1)positive costimulatory pathways:promoting T cell activation, survival and/or differentiation; (2)negative costimulatory pathways:antagonizing TCR signalling and suppressing T cell activation; (3) as third group we will discuss themembers of the TIM family, a rather new family of cell surface molecules involved in the regulation of T cell differentiation and Treg function.Costimulatory pathways have a critical role in the regulation of alloreactivity. A complex network of positive and negative pathways regulates T cell responses. Blocking costimulation improves allograft survival in rodents and non-human primates. The costimulation blocker belatacept is being developed asimmunosuppressivedruginrenal transplantation.

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Track: 12Autoimmunity and Therapathies

Autoimmunityis the system ofimmuneresponsesof an organism against its own cells and tissues. Any disease that results from such an aberrantimmuneresponse is termed an autoimmune disease.

Autoimmunity is present to some extent in everyone and is usually harmless. However, autoimmunity can cause a broad range of human illnesses, known collectively as autoimmune diseases.Autoimmune diseasesoccur when there is progression from benign autoimmunity to pathogenic autoimmunity. This progression is determined by genetic influences as well as environmental triggers. Autoimmunity is evidenced by the presence of autoantibodies (antibodies directed against the person who produced them) and T cells that are reactive with host antigens.

Current treatments for allergic and autoimmune disease treat disease symptoms or depend on non-specific immune suppression. Treatment would be improved greatly by targeting the fundamental cause of the disease, that is the loss of tolerance to an otherwise innocuous antigen in allergy or self-antigen in autoimmune disease (AID). Much has been learned about the mechanisms of peripheral tolerance in recent years. We now appreciate that antigen presenting cells (APC) may be either immunogenic or tolerogenic, depending on their location, environmental cues and activation state

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Track: 13DiagnosticImmunology

Diagnostic Immunology. Immunoassays are laboratory techniques based on the detection of antibody production in response to foreign antigens. Antibodies, part of the humoral immune response, are involved in pathogen detection and neutralization.

Diagnostic immunology has considerably advanced due to the development of automated methods.New technology takes into account saving samples, reagents, and reducing cost.The future of diagnosticimmunologyfaces challenges in the vaccination field for protection against HIV and asanti-cancer therapy. Modern immunology relies heavily on the use of antibodies as highly specific laboratory reagents. The diagnosis of infectious diseases, the successful outcome of transfusions and transplantations, and the availability of biochemical and hematologic assays with extraordinary specificity and sensitivity capabilities all attest to the value of antibody detection.Immunologic methods are used in the treatment and prevention ofinfectious diseasesand in the large number of immune-mediated diseases. Advances in diagnostic immunology are largely driven by instrumentation, automation, and the implementation of less complex and more standardized procedures.

Examples of such processes are as follows:

These methods have facilitated the performance of tests and have greatly expanded the information that can be developed by a clinical laboratory. The tests are now used for clinical diagnosis and the monitoring of therapies and patient responses. Immunology is a relatively young science and there is still so much to discover. Immunologists work in many different disease areas today that include allergy, autoimmunity, immunodeficiency, transplantation, and cancer.

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3nd International Congress on Neuroimmunology and Therapeutics, September 18-19, 2017 Philadelphia, USA; 18thInternational Conference on Immunology (ICI) Dec 12-13, 2016, Bangkok, Thailand; Annual Meeting on Immunology and Immunologist, July 03-05, 2017 Malyasia, Kuala lumpur; 19thInternational Conference on Immunology (ICI) Sept 14-17, 2017, Berlin, Germany; Modelling Viral Infections and Immunity (E1) , May 1 - 4, 2017 | Estes Park, Colorado, USA; 7thInternational Conference on Allergy, Asthma and Clinical Immunology; 18thInternational Conference on Immunology (ICI) Dec 12-13, 2016, Bangkok, Thailand

Track: 14Allergy and Therapathies

Although medications available for allergy are usually very effective, they do not cure people of allergies. Allergenimmunotherapyis the closest thing we have for a "cure" for allergy, reducing the severity of symptoms and the need for medication for many allergy sufferers. Allergen immunotherapy involves the regular administration of gradually increasing doses of allergen extracts over a period of years. Immunotherapy can be given to patients as an injection or as drops or tablets under the tongue (sublingual).Allergen immunotherapy changes the way the immune system reacts to allergens, by switching off allergy. The end result is that you become immune to the allergens, so that you can tolerate them with fewer or no symptoms. Allergen immunotherapy is not, however, a quick fix form of treatment. Those agreeing to allergen immunotherapy need to be committed to 3-5 years of treatment for it to work, and to cooperate with your doctor to minimize the frequency of side effects.Allergen immunotherapyis usually recommended for the treatment of potentially life threatening allergic reactions to stinging insects. Published data on allergen immunotherapy injections shows that venom immunotherapy can reduce the risk of a severe reaction in adults from around 60 % per sting, down to less than 10%. In Australia and New Zealand,venom immunotherapyis currently available for bee and wasp allergy. Jack Jumper Ant immunotherapy is available in Tasmania for Tasmanian residents. Allergen immunotherapy is often recommended for treatment ofallergic rhinitis

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Molecular Immunology & Immunogenetics Congress, March 20-21, 2017 Rome, Italy; 3nd International Congress on Neuroimmunology and Therapeutics, September 18-19, 2017 Philadelphia, USA; 18thInternational Conference on Immunology (ICI) Dec 12-13, 2016, Bangkok, Thailand; Annual Meeting on Immunology and Immunologist, July 03-05, 2017 Malyasia, Kuala lumpur; 19thInternational Conference on Immunology (ICI) Sept 14-17, 2017, Berlin, Germany; Modelling Viral Infections and Immunity (E1) , May 1 - 4, 2017 | Estes Park, Colorado, USA; 7thInternational Conference on Allergy, Asthma and Clinical Immunology; 18thInternational Conference on Immunology (ICI) Dec 12-13, 2016, Bangkok, Thailand

Track: 15Technological Innovations inImmunology

Immunology is the branch of biomedical sciences concerned with all aspects of the immune system in all multicellular organisms. Immunology deals with physiological functioning of the immune system in states of both health and disease as well as malfunctions of the immune system in immunological disorders like allergies, hypersensitivities, immune deficiency, transplant rejection andautoimmune disorders.

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9thworld congress & expo on Immunology, Oct 02-04, 2017, Toronto, Canada; 3rdAntibodies and Bio Therapeutics Congress, November 02-03, 2017 Las Vegas, USA; Molecular Immunology & Immunogenetics Congress, March 20-21, 2017 Rome, Italy; Annual Meeting on Immunology and Immunologist, July 03-05, 2017 Malyasia, Kuala lumpur; 3rd International Congress on Neuroimmunology and Therapeutics, September 18-19, 2017 Philadelphia, USA; 2nd Autoimmunity Conference, Nov 9-10, 2017 Madrid, Spain; Integrating Metabolism and Immunity , May 29 - June 2, 2017 | Dublin, Ireland; American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting, March 03-06, 2017, Atlanta, Georgia

Track:16Antigen Processing

Antigen processingis an immunologicalprocessthat prepares antigensfor presentation to special cells of the immune system called T lymphocytes. It is considered to be a stage ofantigenpresentation pathways. The process by which antigen-presenting cells digest proteins from inside or outside the cell and display the resulting antigenic peptide fragments on cell surface MHC molecules for recognition by T cells is central to the body's ability to detect signs of infection or abnormal cell growth. As such, understanding the processes and mechanisms of antigen processing and presentation provides us with crucial insights necessary for the design ofvaccines and therapeutic strategiesto bolster T-cell responses.

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3rdAntibodies and Bio Therapeutics Congress, November 02-03, 2017 Las Vegas, USA; Molecular Immunology & Immunogenetics Congress, March 20-21, 2017 Rome, Italy; Annual Meeting on Immunology and Immunologist, July 03-05, 2017 Malyasia, Kuala lumpur; 3rd International Congress on Neuroimmunology and Therapeutics, September 18-19, 2017 Philadelphia, USA; 2nd Autoimmunity Conference, Nov 9-10, 2017 Madrid, Spain; Integrating Metabolism and Immunity , May 29 - June 2, 2017 | Dublin, Ireland; American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting, March 03-06, 2017, Atlanta, Georgia

Track: 17Immunoinformatics and Systems Immunology

Immunoinformaticsis a branch ofbioinformaticsdealing with in silico analysis and modelling of immunological data and problems Immunoinformatics includes the study and design of algorithms for mapping potential B- andT-cell epitopes, which lessens the time and cost required for laboratory analysis of pathogen gene products. Using this information, an immunologist can explore the potential binding sites, which, in turn, leads to the development of newvaccines. This methodology is termed reversevaccinology and it analyses the pathogen genome to identify potential antigenic proteins.This is advantageous because conventional methods need to cultivate pathogen and then extract its antigenic proteins. Although pathogens grow fast, extraction of their proteins and then testing of those proteins on a large scale is expensive and time consuming. Immunoinformatics is capable of identifying virulence genes and surface-associated proteins.

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9thworld congress & expo on Immunology, Oct 02-04, 2017, Toronto, Canada; 3rdAntibodies and Bio Therapeutics Congress, November 02-03, 2017 Las Vegas, USA; Molecular Immunology & Immunogenetics Congress, March 20-21, 2017 Rome, Italy; 3nd International Congress on Neuroimmunology and Therapeutics, September 18-19, 2017 Philadelphia, USA; 18th International Conference on Immunology (ICI) Dec 12-13, 2016, Bangkok, Thailand; Annual Meeting on Immunology and Immunologist, July 03-05, 2017 Malyasia, Kuala lumpur; British Society for Immunology Congress, Dec 06-09, 2016, Liverpool, United Kingdom; 7thInternational Conference on Allergy, Asthma and Clinical Immunology; Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology (C7), March 19 - 23, 2017, Whistler, British Columbia, Canada

Track: 18Rheumatology

Rheumatology represents a subspecialty in internal medicine and pediatrics, which is devoted to adequate diagnosis andtherapy of rheumatic diseases(including clinical problems in joints, soft tissues, heritable connective tissue disorders, vasculitis and autoimmune diseases). This field is multidisciplinary in nature, which means it relies on close relationships with other medical specialties.The specialty of rheumatology has undergone a myriad of noteworthy advances in recent years, especially if we consider the development of state-of-the-art biological drugs with novel targets, made possible by rapid advances in the basic science of musculoskeletal diseases and improved imaging techniques.

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Track: 19Nutritional Immunology

Nutritional immunologyis an emerging discipline that evolved with the study of the detrimental effect of malnutrition on the immune system. The clinical and public health importance of nutritional immunology is also receiving attention. Immune system dysfunctions that result from malnutrition are, in fact, NutritionallyAcquired Immune Deficiency Syndromes(NAIDS). NAIDS afflicts millions of people in the Third World, as well as thousands in modern centers, i.e., patients with cachexia secondary to serious disease, neoplasia or trauma. The human immune system functions to protect the body against foreign pathogens and thereby preventing infection and disease. Optimal functioning of the immune system, both innate and adaptive immunity, is strongly influenced by an individuals nutritional status, with malnutrition being the most common cause of immunodeficiency in the world. Nutrient deficiencies result in immunosuppression and dysregulation of the immune response including impairment of phagocyte function and cytokine production, as well as adversely affecting aspects of humoral and cell-mediated immunity. Such alterations in immune function and the resulting inflammation are not only associated with infection, but also with the development of chronic diseases including cancer, autoimmune disease, osteoporosis, disorders of the endocrine system andcardiovascular disease.

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8 - OMICS International Conference

Hematopoietic stem cell transplantation – Wikipedia

Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood.[1][2] It may be autologous (the patient's own stem cells are used), allogeneic (the stem cells come from a donor) or syngeneic (from an identical twin).[1][2] It is a medical procedure in the field of hematology, most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia.[2] In these cases, the recipient's immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease are major complications of allogeneic HSCT.[2]

Hematopoietic stem cell transplantation remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As survival following the procedure has increased, its use has expanded beyond cancer, such as autoimmune diseases.[3][4]

Indications for stem cell transplantation are as follows:

Many recipients of HSCTs are multiple myeloma[5] or leukemia patients[6] who would not benefit from prolonged treatment with, or are already resistant to, chemotherapy. Candidates for HSCTs include pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia with defective stem cells, and also children or adults with aplastic anemia[7] who have lost their stem cells after birth. Other conditions[8] treated with stem cell transplants include sickle-cell disease, myelodysplastic syndrome, neuroblastoma, lymphoma, Ewing's sarcoma, desmoplastic small round cell tumor, chronic granulomatous disease and Hodgkin's disease. More recently non-myeloablative, "mini transplant(microtransplantation)," procedures have been developed that require smaller doses of preparative chemo and radiation. This has allowed HSCT to be conducted in the elderly and other patients who would otherwise be considered too weak to withstand a conventional treatment regimen.

In 2006 a total of 50,417 first hematopoietic stem cell transplants were reported as taking place worldwide, according to a global survey of 1327 centers in 71 countries conducted by the Worldwide Network for Blood and Marrow Transplantation. Of these, 28,901 (57 percent) were autologous and 21,516 (43 percent) were allogeneic (11,928 from family donors and 9,588 from unrelated donors). The main indications for transplant were lymphoproliferative disorders (54.5 percent) and leukemias (33.8 percent), and the majority took place in either Europe (48 percent) or the Americas (36 percent).[9]

In 2014, according to the World Marrow Donor Association, stem cell products provided for unrelated transplantation worldwide had increased to 20,604 (4,149 bone marrow donations, 12,506 peripheral blood stem cell donations, and 3,949 cord blood units).[10]

Autologous HSCT requires the extraction (apheresis) of haematopoietic stem cells (HSC) from the patient and storage of the harvested cells in a freezer. The patient is then treated with high-dose chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population at the cost of partial or complete bone marrow ablation (destruction of patient's bone marrow's ability to grow new blood cells). The patient's own stored stem cells are then transfused into his/her bloodstream, where they replace destroyed tissue and resume the patient's normal blood cell production. Autologous transplants have the advantage of lower risk of infection during the immune-compromised portion of the treatment since the recovery of immune function is rapid. Also, the incidence of patients experiencing rejection (and graft-versus-host disease is impossible) is very rare due to the donor and recipient being the same individual. These advantages have established autologous HSCT as one of the standard second-line treatments for such diseases as lymphoma.[11]

However, for other cancers such as acute myeloid leukemia, the reduced mortality of the autogenous relative to allogeneic HSCT may be outweighed by an increased likelihood of cancer relapse and related mortality, and therefore the allogeneic treatment may be preferred for those conditions.[12] Researchers have conducted small studies using non-myeloablative hematopoietic stem cell transplantation as a possible treatment for type I (insulin dependent) diabetes in children and adults. Results have been promising; however, as of 2009[update] it was premature to speculate whether these experiments will lead to effective treatments for diabetes.[13]

Allogeneics HSCT involves two people: the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more loci of the HLA gene, and a perfect match at these loci is preferred. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely HLA matched sibling), syngeneic (a monozygotic or 'identical' twin of the patient - necessarily extremely rare since few patients have an identical twin, but offering a source of perfectly HLA matched stem cells) or unrelated (donor who is not related and found to have very close degree of HLA matching). Unrelated donors may be found through a registry of bone marrow donors such as the National Marrow Donor Program. People who would like to be tested for a specific family member or friend without joining any of the bone marrow registry data banks may contact a private HLA testing laboratory and be tested with a mouth swab to see if they are a potential match.[14] A "savior sibling" may be intentionally selected by preimplantation genetic diagnosis in order to match a child both regarding HLA type and being free of any obvious inheritable disorder. Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells. In general, by transfusing healthy stem cells to the recipient's bloodstream to reform a healthy immune system, allogeneic HSCTs appear to improve chances for cure or long-term remission once the immediate transplant-related complications are resolved.[15][16][17]

A compatible donor is found by doing additional HLA-testing from the blood of potential donors. The HLA genes fall in two categories (Type I and Type II). In general, mismatches of the Type-I genes (i.e. HLA-A, HLA-B, or HLA-C) increase the risk of graft rejection. A mismatch of an HLA Type II gene (i.e. HLA-DR, or HLA-DQB1) increases the risk of graft-versus-host disease. In addition a genetic mismatch as small as a single DNA base pair is significant so perfect matches require knowledge of the exact DNA sequence of these genes for both donor and recipient. Leading transplant centers currently perform testing for all five of these HLA genes before declaring that a donor and recipient are HLA-identical.

Race and ethnicity are known to play a major role in donor recruitment drives, as members of the same ethnic group are more likely to have matching genes, including the genes for HLA.[18]

As of 2013[update], there were at least two commercialized allogeneic cell therapies, Prochymal and Cartistem.[19]

To limit the risks of transplanted stem cell rejection or of severe graft-versus-host disease in allogeneic HSCT, the donor should preferably have the same human leukocyte antigens (HLA) as the recipient. About 25 to 30 percent of allogeneic HSCT recipients have an HLA-identical sibling. Even so-called "perfect matches" may have mismatched minor alleles that contribute to graft-versus-host disease.

In the case of a bone marrow transplant, the HSC are removed from a large bone of the donor, typically the pelvis, through a large needle that reaches the center of the bone. The technique is referred to as a bone marrow harvest and is performed under general anesthesia.

Peripheral blood stem cells[20] are now the most common source of stem cells for HSCT. They are collected from the blood through a process known as apheresis. The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that removes white blood cells. The red blood cells are returned to the donor. The peripheral stem cell yield is boosted with daily subcutaneous injections of Granulocyte-colony stimulating factor, serving to mobilize stem cells from the donor's bone marrow into the peripheral circulation.

It is also possible to extract stem cells from amniotic fluid for both autologous or heterologous use at the time of childbirth.

Umbilical cord blood is obtained when a mother donates her infant's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSC than is normally found in adult blood. However, the small quantity of blood obtained from an Umbilical Cord (typically about 50 mL) makes it more suitable for transplantation into small children than into adults. Newer techniques using ex-vivo expansion of cord blood units or the use of two cord blood units from different donors allow cord blood transplants to be used in adults.

Cord blood can be harvested from the Umbilical Cord of a child being born after preimplantation genetic diagnosis (PGD) for human leucocyte antigen (HLA) matching (see PGD for HLA matching) in order to donate to an ill sibling requiring HSCT.

Unlike other organs, bone marrow cells can be frozen (cryopreserved) for prolonged periods without damaging too many cells. This is a necessity with autologous HSC because the cells must be harvested from the recipient months in advance of the transplant treatment. In the case of allogeneic transplants, fresh HSC are preferred in order to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. To cryopreserve HSC, a preservative, DMSO, must be added, and the cells must be cooled very slowly in a controlled-rate freezer to prevent osmotic cellular injury during ice crystal formation. HSC may be stored for years in a cryofreezer, which typically uses liquid nitrogen.

The chemotherapy or irradiation given immediately prior to a transplant is called the conditioning regimen, the purpose of which is to help eradicate the patient's disease prior to the infusion of HSC and to suppress immune reactions. The bone marrow can be ablated (destroyed) with dose-levels that cause minimal injury to other tissues. In allogeneic transplants a combination of cyclophosphamide with total body irradiation is conventionally employed. This treatment also has an immunosuppressive effect that prevents rejection of the HSC by the recipient's immune system. The post-transplant prognosis often includes acute and chronic graft-versus-host disease that may be life-threatening. However, in certain leukemias this can coincide with protection against cancer relapse owing to the graft versus tumor effect.[21]Autologous transplants may also use similar conditioning regimens, but many other chemotherapy combinations can be used depending on the type of disease.

A newer treatment approach, non-myeloablative allogeneic transplantation, also termed reduced-intensity conditioning (RIC), uses doses of chemotherapy and radiation too low to eradicate all the bone marrow cells of the recipient.[22]:320321 Instead, non-myeloablative transplants run lower risks of serious infections and transplant-related mortality while relying upon the graft versus tumor effect to resist the inherent increased risk of cancer relapse.[23][24] Also significantly, while requiring high doses of immunosuppressive agents in the early stages of treatment, these doses are less than for conventional transplants.[25] This leads to a state of mixed chimerism early after transplant where both recipient and donor HSC coexist in the bone marrow space.

Decreasing doses of immunosuppressive therapy then allows donor T-cells to eradicate the remaining recipient HSC and to induce the graft versus tumor effect. This effect is often accompanied by mild graft-versus-host disease, the appearance of which is often a surrogate marker for the emergence of the desirable graft versus tumor effect, and also serves as a signal to establish an appropriate dosage level for sustained treatment with low levels of immunosuppressive agents.

Because of their gentler conditioning regimens, these transplants are associated with a lower risk of transplant-related mortality and therefore allow patients who are considered too high-risk for conventional allogeneic HSCT to undergo potentially curative therapy for their disease. The optimal conditioning strategy for each disease and recipient has not been fully established, but RIC can be used in elderly patients unfit for myeloablative regimens, for whom a higher risk of cancer relapse may be acceptable.[22][24]

After several weeks of growth in the bone marrow, expansion of HSC and their progeny is sufficient to normalize the blood cell counts and re-initiate the immune system. The offspring of donor-derived hematopoietic stem cells have been documented to populate many different organs of the recipient, including the heart, liver, and muscle, and these cells had been suggested to have the abilities of regenerating injured tissue in these organs. However, recent research has shown that such lineage infidelity does not occur as a normal phenomenon[citation needed].

HSCT is associated with a high treatment-related mortality in the recipient (1 percent or higher)[citation needed], which limits its use to conditions that are themselves life-threatening. Major complications are veno-occlusive disease, mucositis, infections (sepsis), graft-versus-host disease and the development of new malignancies.

Bone marrow transplantation usually requires that the recipient's own bone marrow be destroyed ("myeloablation"). Prior to "engraftment" patients may go for several weeks without appreciable numbers of white blood cells to help fight infection. This puts a patient at high risk of infections, sepsis and septic shock, despite prophylactic antibiotics. However, antiviral medications, such as acyclovir and valacyclovir, are quite effective in prevention of HSCT-related outbreak of herpetic infection in seropositive patients.[26] The immunosuppressive agents employed in allogeneic transplants for the prevention or treatment of graft-versus-host disease further increase the risk of opportunistic infection. Immunosuppressive drugs are given for a minimum of 6-months after a transplantation, or much longer if required for the treatment of graft-versus-host disease. Transplant patients lose their acquired immunity, for example immunity to childhood diseases such as measles or polio. For this reason transplant patients must be re-vaccinated with childhood vaccines once they are off immunosuppressive medications.

Severe liver injury can result from hepatic veno-occlusive disease (VOD). Elevated levels of bilirubin, hepatomegaly and fluid retention are clinical hallmarks of this condition. There is now a greater appreciation of the generalized cellular injury and obstruction in hepatic vein sinuses, and hepatic VOD has lately been referred to as sinusoidal obstruction syndrome (SOS). Severe cases of SOS are associated with a high mortality rate. Anticoagulants or defibrotide may be effective in reducing the severity of VOD but may also increase bleeding complications. Ursodiol has been shown to help prevent VOD, presumably by facilitating the flow of bile.

The injury of the mucosal lining of the mouth and throat is a common regimen-related toxicity following ablative HSCT regimens. It is usually not life-threatening but is very painful, and prevents eating and drinking. Mucositis is treated with pain medications plus intravenous infusions to prevent dehydration and malnutrition.

Graft-versus-host disease (GVHD) is an inflammatory disease that is unique to allogeneic transplantation. It is an attack of the "new" bone marrow's immune cells against the recipient's tissues. This can occur even if the donor and recipient are HLA-identical because the immune system can still recognize other differences between their tissues. It is aptly named graft-versus-host disease because bone marrow transplantation is the only transplant procedure in which the transplanted cells must accept the body rather than the body accepting the new cells.[27]

Acute graft-versus-host disease typically occurs in the first 3 months after transplantation and may involve the skin, intestine, or the liver. High-dose corticosteroids such as prednisone are a standard treatment; however this immuno-suppressive treatment often leads to deadly infections. Chronic graft-versus-host disease may also develop after allogeneic transplant. It is the major source of late treatment-related complications, although it less often results in death. In addition to inflammation, chronic graft-versus-host disease may lead to the development of fibrosis, or scar tissue, similar to scleroderma; it may cause functional disability and require prolonged immunosuppressive therapy. Graft-versus-host disease is usually mediated by T cells, which react to foreign peptides presented on the MHC of the host.[citation needed]

Graft versus tumor effect (GVT) or "graft versus leukemia" effect is the beneficial aspect of the Graft-versus-Host phenomenon. For example, HSCT patients with either acute, or in particular chronic, graft-versus-host disease after an allogeneic transplant tend to have a lower risk of cancer relapse.[28][29] This is due to a therapeutic immune reaction of the grafted donor T lymphocytes against the diseased bone marrow of the recipient. This lower rate of relapse accounts for the increased success rate of allogeneic transplants, compared to transplants from identical twins, and indicates that allogeneic HSCT is a form of immunotherapy. GVT is the major benefit of transplants that do not employ the highest immuno-suppressive regimens.

Graft versus tumor is mainly beneficial in diseases with slow progress, e.g. chronic leukemia, low-grade lymphoma, and some cases multiple myeloma. However, it is less effective in rapidly growing acute leukemias.[30]

If cancer relapses after HSCT, another transplant can be performed, infusing the patient with a greater quantity of donor white blood cells (Donor lymphocyte infusion).[30]

Patients after HSCT are at a higher risk for oral carcinoma. Post-HSCT oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-HSCT patients.[31]

Prognosis in HSCT varies widely dependent upon disease type, stage, stem cell source, HLA-matched status (for allogeneic HSCT) and conditioning regimen. A transplant offers a chance for cure or long-term remission if the inherent complications of graft versus host disease, immuno-suppressive treatments and the spectrum of opportunistic infections can be survived.[15][16] In recent years, survival rates have been gradually improving across almost all populations and sub-populations receiving transplants.[32]

Mortality for allogeneic stem cell transplantation can be estimated using the prediction model created by Sorror et al.,[33] using the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). The HCT-CI was derived and validated by investigators at the Fred Hutchinson Cancer Research Center (Seattle, WA). The HCT-CI modifies and adds to a well-validated comorbidity index, the Charlson Comorbidity Index (CCI) (Charlson et al.[34]) The CCI was previously applied to patients undergoing allogeneic HCT but appears to provide less survival prediction and discrimination than the HCT-CI scoring system.

The risks of a complication depend on patient characteristics, health care providers and the apheresis procedure, and the colony-stimulating factor used (G-CSF). G-CSF drugs include filgrastim (Neupogen, Neulasta), and lenograstim (Graslopin).

Filgrastim is typically dosed in the 10 microgram/kg level for 45 days during the harvesting of stem cells. The documented adverse effects of filgrastim include splenic rupture (indicated by left upper abdominal or shoulder pain, risk 1 in 40000), Adult respiratory distress syndrome (ARDS), alveolar hemorrage, and allergic reactions (usually expressed in first 30 minutes, risk 1 in 300).[35][36][37] In addition, platelet and hemoglobin levels dip post-procedure, not returning to normal until one month.[37]

The question of whether geriatrics (patients over 65) react the same as patients under 65 has not been sufficiently examined. Coagulation issues and inflammation of atherosclerotic plaques are known to occur as a result of G-CSF injection. G-CSF has also been described to induce genetic changes in mononuclear cells of normal donors.[36] There is evidence that myelodysplasia (MDS) or acute myeloid leukaemia (AML) can be induced by GCSF in susceptible individuals.[38]

Blood was drawn peripherally in a majority of patients, but a central line to jugular/subclavian/femoral veins may be used in 16 percent of women and 4 percent of men. Adverse reactions during apheresis were experienced in 20 percent of women and 8 percent of men, these adverse events primarily consisted of numbness/tingling, multiple line attempts, and nausea.[37]

A study involving 2408 donors (1860 years) indicated that bone pain (primarily back and hips) as a result of filgrastim treatment is observed in 80 percent of donors by day 4 post-injection.[37] This pain responded to acetaminophen or ibuprofen in 65 percent of donors and was characterized as mild to moderate in 80 percent of donors and severe in 10 percent.[37] Bone pain receded post-donation to 26 percent of patients 2 days post-donation, 6 percent of patients one week post-donation, and

In one metastudy that incorporated data from 377 donors, 44 percent of patients reported having adverse side effects after peripheral blood HSCT.[38] Side effects included pain prior to the collection procedure as a result of GCSF injections, post-procedural generalized skeletal pain, fatigue and reduced energy.[38]

A study that surveyed 2408 donors found that serious adverse events (requiring prolonged hospitalization) occurred in 15 donors (at a rate of 0.6 percent), although none of these events were fatal.[37] Donors were not observed to have higher than normal rates of cancer with up to 48 years of follow up.[37] One study based on a survey of medical teams covered approximately 24,000 peripheral blood HSCT cases between 1993 and 2005, and found a serious cardiovascular adverse reaction rate of about 1 in 1500.[36] This study reported a cardiovascular-related fatality risk within the first 30 days HSCT of about 2 in 10000. For this same group, severe cardiovascular events were observed with a rate of about 1 in 1500. The most common severe adverse reactions were pulmonary edema/deep vein thrombosis, splenic rupture, and myocardial infarction. Haematological malignancy induction was comparable to that observed in the general population, with only 15 reported cases within 4 years.[36]

Georges Math, a French oncologist, performed the first European bone marrow transplant in November 1958 on five Yugoslavian nuclear workers whose own marrow had been damaged by irradiation caused by a criticality accident at the Vina Nuclear Institute, but all of these transplants were rejected.[39][40][41][42][43] Math later pioneered the use of bone marrow transplants in the treatment of leukemia.[43]

Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology or Medicine. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called graft-versus-host disease.[44]

The first physician to perform a successful human bone marrow transplant on a disease other than cancer was Robert A. Good at the University of Minnesota in 1968.[45] In 1975, John Kersey, M.D., also of the University of Minnesota, performed the first successful bone marrow transplant to cure lymphoma. His patient, a 16-year-old-boy, is today the longest-living lymphoma transplant survivor.[46]

At the end of 2012, 20.2 million people had registered their willingness to be a bone marrow donor with one of the 67 registries from 49 countries participating in Bone Marrow Donors Worldwide. 17.9 million of these registered donors had been ABDR typed, allowing easy matching. A further 561,000 cord blood units had been received by one of 46 cord blood banks from 30 countries participating. The highest total number of bone marrow donors registered were those from the USA (8.0 million), and the highest number per capita were those from Cyprus (15.4 percent of the population).[47]

Within the United States, racial minority groups are the least likely to be registered and therefore the least likely to find a potentially life-saving match. In 1990, only six African-Americans were able to find a bone marrow match, and all six had common European genetic signatures.[48]

Africans are more genetically diverse than people of European descent, which means that more registrations are needed to find a match. Bone marrow and cord blood banks exist in South Africa, and a new program is beginning in Nigeria.[48] Many people belonging to different races are requested to donate as there is a shortage of donors in African, Mixed race, Latino, Aboriginal, and many other communities.

In 2007, a team of doctors in Berlin, Germany, including Gero Htter, performed a stem cell transplant for leukemia patient Timothy Ray Brown, who was also HIV-positive.[49] From 60 matching donors, they selected a [CCR5]-32 homozygous individual with two genetic copies of a rare variant of a cell surface receptor. This genetic trait confers resistance to HIV infection by blocking attachment of HIV to the cell. Roughly one in 1000 people of European ancestry have this inherited mutation, but it is rarer in other populations.[50][51] The transplant was repeated a year later after a leukemia relapse. Over three years after the initial transplant, and despite discontinuing antiretroviral therapy, researchers cannot detect HIV in the transplant recipient's blood or in various biopsies of his tissues.[52] Levels of HIV-specific antibodies have also declined, leading to speculation that the patient may have been functionally cured of HIV. However, scientists emphasise that this is an unusual case.[53] Potentially fatal transplant complications (the "Berlin patient" suffered from graft-versus-host disease and leukoencephalopathy) mean that the procedure could not be performed in others with HIV, even if sufficient numbers of suitable donors were found.[54][55]

In 2012, Daniel Kuritzkes reported results of two stem cell transplants in patients with HIV. They did not, however, use donors with the 32 deletion. After their transplant procedures, both were put on antiretroviral therapies, during which neither showed traces of HIV in their blood plasma and purified CD4 T cells using a sensitive culture method (less than 3 copies/mL). However, the virus was once again detected in both patients some time after the discontinuation of therapy.[56]

Since McAllister's 1997 report on a patient with multiple sclerosis (MS) who received a bone marrow transplant for CML,[57] over 600 reports have been published describing HSCTs performed primarily for MS.[58] These have been shown to "reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients" that have aggressive highly active MS, "in the absence of chronic treatment with disease-modifying agents".[58]

Clincs performing HSCT includes Northwestern University and Karolinska University Hospital.

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Hematopoietic stem cell transplantation - Wikipedia