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Archive for the ‘Bone Marrow Stem Cells’ Category

Bone Marrow – What Does Bone Marrow Do? – Health News

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Bone Marrow – What Does Bone Marrow Do? – Health News

New therapy could protect diabetic bones – Science Magazine

A new therapy changes the balance of osteoblasts (pictured here) and fat cells in the bone marrow, leading to stronger bones.

Science Picture Co/Science Source

By Emma YasinskiSep. 5, 2017 , 2:59 PM

A drug that can reverse diabetes and obesity in mice may have an unexpected benefit: strengthening bones. Experiments with a compound called TNP (2,4,6-trinitrophenol, which is also known as picric acid), which researchers often use to study obesity and diabetes, show that in mice the therapy can promote the formation of new bone. Thats in contrast to many diabetes drugs currently in wide use that leave patients bones weaker. If TNP has similar effects in humans, it may even be able to stimulate bone growth after fractures or prevent bone loss due to aging or disuse.

As more and more patients successfully manage diabetes with drugs that increase their insulin sensitivity, doctors and researchers have observed a serious problem: Thedrugs seem to decrease the activity of cells that produce bone, leaving patients prone to fractures and osteoporosis.

There are millions and millions of people that have osteoporosis [with or without diabetes], and it’s not something we can cure, says Sean Morrison, a stem cell researcher at University of Texas Southwestern in Dallas. We need new agents that promote bone formation.

Morrison and his colleagues have shown that a high-fat diet causes mice to develop bones that contain more fat and less bone. The diet increased the levels of leptina hormone produced by fat cells that usually signals satiety in the brainin the bone marrow, which promoted the development of fat cells instead of bone cells. That suggests that nutrition has a direct effect on the balance of bone and fat in the bone marrow.

After reading Morrisons work, Siddaraju Boregowda, a stem cell researcher at the Scripps Research Institute in Jupiter, Florida, was reminded of genetically altered mice that dont gain body fat or develop diabetes, even when fed high-fat diets. He and his boss, stem cell researcher Donald Phinney, wondered whetherthose mice were also protected from the fattening of the bone marrow that accompanies a high-fat diet.

They contacted Anutosh Chakraborty, a molecular biologist who was studying such mice down the hall at Scripps at the time. The animals lack the gene for an enzyme called inositol hexakisphosphate kinase 1 (IP6K1), which is known to play a role in fat accumulation and insulin sensitivity. The scientists suspected that the lost enzyme might affect the animals’ mesenchymal stem cells (MSCs)stem cells found in the bone marrow that are capable of developing into both thebone cells and fat cells that make up our skeletons. If too many fat cells develop, they take the place of bone cells, weakening the bone.

The researchers fed genetically altered and normal mice a high-fat diet for 8weeks. Not only did the genetically altered mice develop fewer fat cells than their normal counterparts, but their production of bone cells was higher than that of the normal mice, the team reported last month in Stem Cells.

The scientists then set out to see whetherthey could use a drug to achieve the same effect in normal mice. For 8weeks, they fed normal mice a high-fat diet and gave them daily injections of either TNP, a well-known IP6K1 inhibitor, or a placebo. When they analyzed the animals bones and marrow, they found that mice that had received TNP had significantly more bone cells, fewer fat cells, and greater overall bone area. The IP6K1 inhibitor apparently protected the mice from the detrimental effects of the high-fat diet.

The study provided thesurprising result that one new therapy currently being explored to lower insulin resistance promotes, rather than decreases, the formation of bone in mice, says DarwinProckop,a stem cell researcher at Texas A&M College of Medicine in Temple, who was not involved in the work.

The researchers still need to figure out how to deliver TNPs effects only to MSCs, instead of the entire body, given that it sometimes blocks other enzymes along with IP6K1. Inhibition of IP6K1 is a promising target for patients with both diabetes and obesity, Boregowda says. He says he and his colleagues are now enthusiastic about testing their findings in a wide range of bone-related diseases and disorders. It might even help heal broken bones, he speculates.

Phinney, on the other hand, is aiming even higher. He wonders whetherthe therapy could also be useful for space travel, because bones are especially vulnerable to deterioration in zero gravity. Its a whole new field of science and drug discovery.

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New therapy could protect diabetic bones – Science Magazine

Stem Cell Therapy: A Lethal Cure – Medical News Bulletin

Stem cell therapy is a two-step process. First, the patients blood cells are destroyed by chemotherapy, radiation therapy or immunosuppression. This conditioning process also eradicates any cancer cells that survived first-line treatment. Second, the patient receives stem cells harvested from a donors bone marrow or peripheral blood (circulating blood). While this can be an effective cure, it can cause graft-versus-host disease (GVHD) in up to 50% of patients. GVHD is more likely to develop in patients who have received a peripheral blood transplant and can kill 15%-20% of patients.

Two types of GVHD can develop, acute and chronic, and patients may develop either one, both or neither type. GVHD is less likely to occur and symptoms are milder if the donor cells closely match those of the patient. Acute GVHD can develop within 100 days of a transplant. The first step of stem cell therapy can cause tissue damage, and bacteria from the gut can escape into the bloodstream. This primes the patients antigen-presenting cells (cells that activate the immune response), which subsequently encourage donor T cells to proliferate and attack the patients tissues. Symptoms include vomiting, diarrhea, skin rashes, nausea, vomiting and liver problems. This can be resolved relatively quickly in one third of patients using immunosuppressive treatments, but some patients can progress to chronic GVHD.

The biological mechanisms responsible for chronic GVHD are not completely understood, but scientists believe that other immune system cells from the donor (B cells and macrophages) are stimulated and damage the patients tissues. Symptoms include dry eyes, mouth sores, muscle weakness, fatigue and joint problems.

Unfortunately, development of effective treatments for GVHD is not keeping up with the increasing number of GVHD patients or with advances in understanding this disease. At present, standard treatments include corticosteroids and drugs that reduce IL-2, an immune system chemical that helps T-cells multiply and diversify. These treatments have various side effects including suppressing the patients immune system, thereby increasing risk of infection.

One challenge stalling drug research is that a small degree of graft-versus-host response must occur for successful stem cell therapy: donor cells will destroy any cancer cells that remain after the first stage of therapy. This challenge is discussed in a recent article in Science Health.Although several treatments have been trialed, success is variable and often targets only acute GVHD or chronic GVHD. Biomarkers have also been detected that may help identify individuals at risk of developing severe GVHD, information that may aid the development of personalized treatment strategies. Drugs that have been approved for other diseases, but not for GVHD, show promise and include ibrutinib for chronic GVHD (approved for specific blood cancers) and ruxolitinib for acute GVHD (approved for bone marrow disorders).

The impact of stem cell therapy must not be underestimated: up to 50% of recipients will develop GVHD. Unfortunately, some individuals will develop chronic GVHD, a condition that is just as difficult to survive as cancer. This highlights the importance of developing continued care strategies for individuals receiving stem cell therapy as a final defence against cancer.

Written byNatasha Tetlow, PhD

Reference: Cohen J. A stem cell transplant helped beat back a young doctors cancer. Now, its assaulting his body. Science Health. 2017. Available at: DOI: 10.1126/science.aan7079

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Stem Cell Therapy: A Lethal Cure – Medical News Bulletin

Appeal to help firefighter battling cancer caused by clinical trial for Crohn’s disease – Deadline News

A VETERAN firefighter is battling blood cancer caused by taking part in a trial of a new treatment for his Crohns disease.Gary Dall, who has spent almost 30 years saving lives, has an aggressive form of myelodysplasia (MDS) a type of cancer where the bone marrow fails to make enough healthy blood cells.The 49-year-old from Kirkcaldy, Fife, agreed to take part in a clinical trial to cure his Crohns disease seven years ago.Gary says he was advised there was a low risk of developing cancer as a result of the treatment, which involved a transplant of his own stem cells, taking medication and undergoing chemotherapy.Last year, doctors discovered the father-of-fours blood count was low and bone marrow tests showed that he had MDS.The only cure for Gary is for him is to have a second stem cell transplant which he can only have when he finds a suitable donor.Now, the Scottish Fire and Rescue Service and blood cancer charity, The Anthony Nolen Trust are holding a public donor event at Kirkcaldy fire station next weekend to find a donor.Gary, a group manager at Kirkcaldy station, was on medication for Crohns, a long-term condition which causes inflammation of the digestive system and currently affects 115,000 people in the UK.Seven years ago, his medication for the disease stopped working.

Gary said today (thu): I was offered a clinical trial and took it. The trial involved taking medication to increase my blood cells and then chemotherapy.They would have told me about the risks involved but with the state I was in, I cant remember much.The risks for something like this are low.Speaking about the appeal for a second stem cell donor he added: Ive been told theres a 60% chance I will find a match because Im white and British so match a lot of people on the register but the more people that donate, the more will help save others lives too.Gary told his local paper this week: It was just one of those things that a treatment for one disease led to me getting another. Its not nice, but Im just taking things as they come and hoping that a match can be found.When we first found out my family were shocked, and it has taken a bit of getting used to.After hearing that fan Gary was in need of a transplant, members from Raith Rovers Football team signed up to a national bone marrow register.Kirkcaldy fire station will be holding a drive on September 16 to encourage members of the public to join a register to potentially become a bone marrow donor.Healthy people, aged between 16 and 30 are eligible to register to become stem cell donors.They will have to fill out a form and provide a saliva sample on the day but are advised not to eat or drink anything half an hour before attending.There is currently no cure for Crohns disease but medics provide treatment to stop the inflammatory process, relieve symptoms and avoid surgery wherever possible.Past research has shown that patients with Crohns disease of the small and/or large intestine have an increased risk of developing cancer at these areas.Gary, who was diagnosed with Crohns disease 13 years ago, today revealed that the treatment puts 95% of patients into remission. Tragically, he has been left with bith Crohns and cancer.He said the trial was offered via NHS Fife. Called Autologous Stem cell Transplantation International Crohns (ASTIC), the treatment has been undergone by crohns sufferers worldwide.

Today Gary said: The medication I was given wasnt working at all so I was told about about the ASTIC trial instead of having to get my bowels removed.It was an attempt to cure it. 95% of people over the world that have had it go into remission. Unfortunately I was one of the five percent that didnt.Gary said his blood cancer is only curable if he gets a matching donor.He added: The drive isnt just about me though, its about everyone else who could be saved by people getting registered as donors.Treatment would involve destroying Garys own bone marrow cells with chemotherapy before having stem cells from a donor fed into his bloodstream via a drip.Amy Bartlett, Register Development Manager for Scotland at the Anthony Nolan Trust, said: We were deeply saddened to learn about Garys diagnosis, and we will support him in every step of his search for a lifesaving donor.Im looking forward to working with our close partners in the SFRS in Kirkcaldy to recruit even more potential lifesavers to the Anthony Nolan register every person who signs up has the potential to help someone like Gary whos in need of a stem cell transplant.We know from the amazing response to Ava Starks appeal for a lifesaving donor how brilliant the people of Fife, and Scotland, are in rallying behind someone in desperate need.

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Appeal to help firefighter battling cancer caused by clinical trial for Crohn’s disease – Deadline News

Convoy from Children’s Hospital to La Caada carries precious cargo a 2-year-old bone marrow recipient – Los Angeles Times

On Saturday morning, a convoy of vintage Ford Broncos carrying some very precious cargo made a stop at La Caadas Descanso Gardens.

En route from Childrens Hospital Los Angeles, the motorcade was led by a golden 1971 Bronco with Thousand Oaks resident Tyler Kelly at the helm. Tucked safely into a car seat in the back was 2-year-old Pierce Kelly, known by family and friends as Fierce Pierce, still recovering from a July 21 bone marrow transplant.

At the La Caada home of relatives Donna and Dave McLaughlin, Pierce will recuperate under the watchful eye of mom Aubrey. For 100 days following the procedure, he must reside within a 30-minute drive of Childrens Hospital for monitoring.

Saturdays 13-mile drive was just one portion of a tumultuous journey the Kellys have been on since April 7, when Pierce was diagnosed with acute myeloid leukemia. His chance of surviving the devastating illness with treatment alone was only 50%, according to mom Aubrey. But there was one hope if the Kellys could find a bone marrow donor, Pierces odds would improve by at least another 15%.

We were at the mercy of whoever had registered, Aubrey Kelly recalled.

Among the nearly 13.5 million Americans already listed as donors on the Be the Match Marrow Registry, there were no donors close enough to be a match with Pierce.

Raquel Edpao, a community outreach specialist for Be the Match, said on any given day there are 14,000 people like the Kellys, searching registries for a bone marrow match. Its her job to help educate people how simple it is to join the registry and to donate if called.

Potential donors register online at bethematch.org, then receive and turn in a cheek swab. After that, theyre contacted if they are a potential match for someone. Edpao estimates about one out of every 430 registrants will be asked to donate.

There are so many misconceptions about donating, she said, invoking myths about spinal drilling, painful extractions and missed days at work. Its usually as simple as donating blood.

In about 20% of cases donors are asked to undergo a marrow extraction, a 45-minute outpatient procedure involving a general anesthetic.

Luckily for the Kellys, a search of donors worldwide returned a single donor in France whose human leukocyte antigen (HLA) protein was a 10-out-of-10 match with Pierces. While the marrow was shipped, the 2-year-old underwent chemotherapy to destroy most of his damaged stem cells in preparation for the donation.

Its a fine balance of leaving him with enough cells to receive the new ones, but not so many that the new cells dont have enough room to grow, Aubrey Kelly said, explaining how her sons blood type switched from A positive, his own type, to the donors O negative.

Pierces recovery from the transplant requires a sterile environment that means he cannot stay with siblings Sierra, 4, and 6-month-old Harper. Donna McLaughlin, a cousin of Aubrey Kellys dad, said she and husband Dave were happy to offer their home in La Caadas Paradise Valley neighborhood for his recovery.

Ive worked for the past week cleaning my house its never been so clean, she said of her preparation for Pierce and Aubreys 57-day visit. Im being paranoid, I know, but he is going to be OK on my watch.

Knowing he would have to return to Thousand Oaks to take care of Pierces sisters, Tyler Kelly wanted to ensure his sons trip from the hospital would be a special one. The Bronco the same vehicle his mother drove to the hospital in 1981 so he could be delivered, and the same one he and Aubrey have used to get to the delivery room in time for the birth of their own three children seemed a fitting conveyance.

We wanted to continue the tradition, he said.

Hoping to assemble a retinue for the drive, Tyler Kelly reached out to enthusiast club SoCal Broncos and classicbroncos.com. Several people responded, including Agoura Hills Bronco owner Dan Bennett, for whom the cause was personal. About 10 years ago he saved a life by donating his own bone marrow.

To be able to go in and help play an intrinsic role in saving someones life is a really special thing, Bennett said. I think everybody should do it.

sara.cardine@latimes.com

Twitter: @SaraCardine

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Convoy from Children’s Hospital to La Caada carries precious cargo a 2-year-old bone marrow recipient – Los Angeles Times

My son died of cancer: Why I’m celebrating his birthday with stem cell awareness – DailyO

Grief is a personal matter.Each of us has our own mechanisms to copethere is no format set in stone, there are no boundaries. For me, the week leading up to my son Arjan Vir’s birthday has always been the most difficult to deal with.

I am overwhelmed by a well of emotions: On the one hand, there are all those happy memories, so much excitement building up to planning those wonderful birthday parties themes to be decided, lists to be made, cards to be distributed, menus, games and oh, the return gifts one mustn’t forget and then this sudden feeling of hollowness, the sinking depths of which words cannot describe.

Beyond words

I lost my 26-year-old son Arjan Vir to Leukaemia in 2012. Arjan was one of those hugely social people with an enviable optimism about him he loved to have people around him and had the enormous ability to attract people, make friends and share his life with them. His friendships were deeply honest and truly meaningful, there was nothing hollow about them. Those around Arjan loved his happy-go-lucky nature and his laidback attitude towards life.

Losing Arjan did not just leave us his family and friends with an irrevocable sense of vacuum, it was felt by the many lives he had touched in some way or the other. Photo:Simi Singh

My son never lost his ability to make friends despite the battle he was fighting with cancer. Arjan had a battalion of friends in the hospital: ward boys, nurses, lab technicians and resident doctors could be seen about his room whenever they had spare time; some asking for advice on which phone to buy, to have the odd computer issue sorted, if nothing else, just to watch him play computer games.

Losing Arjan did not just leave us his family and friends with an irrevocable sense of vacuum, it was felt by the many lives he had touched in some way or the other.

An intensely sensitive child, Arjan worried more about others than himself he was an avid reader, wrote beautiful poetry and had an imagination that went beyond words.

His passion for computer games had pre-determined his career options, he had decided to study computer graphics and 3D computer animation. Even at the hospital, as he underwent treacherous rounds of chemotherapy, cycle after cycle, his imagination worked overtime planning some game or the other based on his treatment.

Knowing BMT

A Leukaemia patient, Arjan needed a bone marrow transplant (BMT). In a layperson’s terms, BMT means that the unhealthy bone marrow is killed under highly sanitised conditions by giving the patient very high doses of chemotherapy and radiation and replaced by a healthy bone marrow. That sounds perfectly simple, but bone marrow transplant remains a complicated and dangerous procedure.

What consequences does that come with?

For the uninitiated, bone marrow is the soft tissue where all our vital blood components RBCs, WBCs, platelets, plasma and stem cells are formed. Killing one’s bone marrow essentially means there is no immunity left to take care of our body.

Where does the healthy bone marrow come from if we are to attempt to rid the body of cancer?

There are two broad types of BMT: Autologous where the unhealthy bone marrow from our body is removed, worked upon or mutated and replaced, and the allogenic transplant in which another person’s healthy bone marrow replaces our own.

With the second type of transplant come incredible complications and the daunting task of finding the donor bone marrow that must replace ours: one needs to find another person whose DNA is identical to ours. The first and most obvious choice, of course, would be a sibling.

However, the chances of finding the identical DNA HLA typing that matches your siblings’ is only 1:4, and if such a match isn’t possible, where do we go?

In Arjan’s case, our younger son’s HLA typing did not match, and the chances of finding an unrelated donor match were one in a million.

This was the worst possible news we could get, worse than the news of Arjan being diagnosed with Leukaemia.

How does one find an identical HLA typing match in this whole world where do you start, whom do you turn to?

[Photo: Weill Cornell Medecine]

Discovering stem cell registry

In 2012, there were no substantial HLA typing registries in India unlike in developed countries, which maintain nationwide registries that are linked to the worldwide bone marrow registry.

The doctors guided us to approach All India Institute of Medical Sciences (AIIMS) while AIIMS did not have a significant registry of its own, it had a membership with the World Marrow Donors Association (WMDA), and hence could do a worldwide search to find an HLA match for Arjan.

However, institutes likeAIIMS have become desensitised to the urgency that such cases demand and we got no response from them.

At the time, Datri in Chennai was the sole functioning stem cell registry it had about 12,000 donors in its data bank, but we did not get a quick response from them either.

Our son’s doctors here told us that we were sitting on a “time bomb” we needed to act swiftly, we could lose no time and that’s when we decided to take Arjan to the US for his further treatment and then, hopefully, a BMT.

Arjan was distressed to discover the situation in India; when he heard about the lack of registries, his first thought was that once he had recovered, he would set up a meaningful registry at home. His biggest concern was: What do the poor do, where do they go?

And so, five years on, the Arjan Vir Foundation was set up in the memory of our very dear son. Our aim is to run a widespread registry that addresses all blood disorders.

We hope to provide assistance at all stages of treatment, recovery, after care, and the rehabilitation and resettlement of patients.

Registering as a donor is easy: any individual over age 18 can become a donor and be a part of the registry till the age of 60, provided they are healthy.

All that one needs is a simple mouth swab test and the consent to donate stem cells when the need arises. The swabs are sent to a highly-specialised laboratory in the US for HLA typing and the results shared with the worldwide registry maintained by WMDA.

Upon finding a match for a patient, the registry contacts the concerned donor.

The process is not complicated, it is exactly like platelet donation, only a few hours longer: avolunteer must undergo a complete medical check-up prior to donating stem cells and is put on stem cell boosting therapy for about four days before the procedure. No incision is involved and the donor does not require hospitalisation.

It just takes one day of your life and busy schedule to save a life.

***

Today, as I sat down to write this article, I also planned another kind of a celebration for Arjan’s birthday on September 6: this year, we are holding a camp to bring about awareness about stem cells and register donors at a university in Noida.

Once again there is excitement, albeit of a different kind one held together with a sense of pathos.

Also read: Memories of my mother that Alzheimer’s can’t wipe clean

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My son died of cancer: Why I’m celebrating his birthday with stem cell awareness – DailyO

U of R hosts stem cell swabbing initiative to help save lives through national database – Globalnews.ca

At just four-years-old, Erica Honoways son has gone through more than most people will experience in a lifetime.

In February 2016, the family received devastating news, her son Lincoln had been diagnosed with bone marrow failure. He was just three years old at the time.

Lincoln needed a bone marrow transplant, and doctors were only able to find two matches in the entire world. The first donor fell through, so Lincoln was left with only one option.

It was terrifying. We didnt know what we were dealing with, Honoway said. We didnt know what the chances were they would find a match for him. Even if they did, we didnt know if he would make it through the transplant, so it was the scariest experience of our lives.

After the blood transfusions, chemotherapy, radiation and bone marrow transplant, Lincoln is now a happy and active four year old, all thanks to an unknown hero.

This person has just been our angel, Honoway said. We love her and we dont even know her. We say her We have a feeling its a woman but we dont know anything about this person. We dont know where in the world they live, we dont know if its a man or a woman, we dont know anything. But all we know is that they are our hero.

Honoway added that they must wait a minimum of two years before they can meet the donor.

Lincolns successful transplant was the reason Honoway and her family were supporting the University of Reginas Get Swabbed event on Monday, to encourage students between the ages of 17 and 35 to get their cheeks swabbed and enter a national stem call database.

I heard about Erica and Lincoln and I just thought it was amazing how someone just saved his life, and she doesnt even know who he is or who she is, I just think its amazing, U of R Stem Cell Club president Sylvia Okonofua said. I felt like if I take up this initiative and actually run drives where people [can get] on the stem cell registry, [it can] help save a life someday.

Getting students involved and realizing their impact of their involvement through something like this was one of the main goals, U of R student engagement co-ordinator Doug OBrien said. Another goal of having todays Get Swabbed initiative was obviously to support the stem cell database for Canada and through the One Match program.

Approximately 80 students took part in Mondays Get Swabbed event, and organizers are hoping to increase that number for the next event on Sept. 14.

Its a simple way to help save a life.

I hope people realize that they have the opportunity to save someones life, imagine what that would feel like, Honoway said. Youd get to know forever that you saved another humans life. Its pretty special.

2017Global News, a division of Corus Entertainment Inc.

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U of R hosts stem cell swabbing initiative to help save lives through national database – Globalnews.ca

Chemo-boosting drug discovered for leukaemia – Drug Target Review – Drug Target Review

Drugs developed to treat heart and blood vessel problems could be used to treat leukaemia

Drugs developed to treat heart and blood vessel problems could be used in combination with chemotherapy to treat an aggressive form of adult leukaemia.

Researchers at the Francis Crick Institute, Kings College London and Barts Cancer Institute discovered that acute myeloid leukaemia (AML) causes bone marrow to leak blood, preventing chemotherapy from being delivered properly.

Drugs that reversed bone marrow leakiness boosted the effect of chemotherapy in mice and human tissue, providing a possible new combination therapy for AML patients.

To study how AML affects bone marrow, the researchers injected mice with bone marrow from AML patients. Later, they compared their bone marrow with healthy mice using a technique called intravital microscopy that allows you to see biological processes in live animals. They found that pre-loaded fluorescent dyes leaked out of the bone marrow blood vessels in AML mice, but not healthy mice.

Next, the team tried to understand what caused the bone marrow in AML mice to become leaky by studying molecular changes in the cells lining the blood vessels. They found that they were oxygen-starved compared to healthy mice, likely because AML cells use up a lot of oxygen in the surrounding tissue. In response to a reduction in oxygen, there was an increase in nitric oxide (NO) production a molecule that usually alerts the body to areas of low oxygen.

As NO is a muscle relaxant, the team suspected that it might be causing bone marrow leakiness by loosening the tight seams between cells, allowing blood to escape through the gaps. By blocking the production of NO using drugs, the team were able to restore bone marrow blood vessels in AML mice, preventing blood from leaking out. Mice given NO blockers in combination with chemotherapy had much slower leukaemia progression and stayed in remission much longer than mice given chemotherapy alone.

When the vessels are leaky, bone marrow blood flow becomes irregular and leukaemia cells can easily find places to hide and escape chemotherapy drugs, said researcher Dr Diana Passaro. Leaky vessels also prevent oxygen reaching parts of the bone marrow, which contributes to more NO production and leakiness.

By restoring normal blood flow with NO blockers, we ensure that chemotherapy actually reaches the leukaemia cells, so that therapy works properly, she added.

In addition to ensuring that chemotherapy drugs reach their targets, the team also found that NO blockers boosted the number of stem cells in the bone marrow. This may also improve treatment outcomes by helping healthy cells to out-compete cancerous cells.

The team also found that bone marrow biopsies from AML patients had higher NO levels than those from healthy donors, and failure to reduce NO levels was associated with chemotherapy failure.

Our findings suggest that it might be possible to predict how well people with AML will respond to chemotherapy, said Dr Dominique Bonnet, senior author of the paper and Group Leader at the Francis Crick Institute.

Weve uncovered a biological marker for this type of leukaemia as well as a possible drug target. The next step will be clinical trials to see if NO blockers can help AML patients as much as our pre-clinical experiments suggest.

We found that the cancer was damaging the walls of blood vessels responsible for delivering oxygen, nutrients, and chemotherapy. When we used drugs to stop the leaks in mice, we were able to kill the cancer using conventional chemotherapy, said Dr Passaro. As the drugs are already in clinical trials for other conditions, it is hoped that they could be given the green light for AML patients in the future.

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Chemo-boosting drug discovered for leukaemia – Drug Target Review – Drug Target Review

Bone marrow transplant on record run in SCB Medical College and Hospital at Cuttack – The New Indian Express

Bishnupriya Nayak at BMT unit after bone marrow transplantation | Express

BHUBANESWAR: The Haematology Department of SCB Medical College and Hospital (SCBMCH) at Cuttack has notched up a record of sorts and achieved a new milestone in the country by performing 50 bone marrow transplantations in just over three years.

The special Bone Marrow Transplant (BMT) unit started in February 2014 has conducted its 50th procedure on Bishnupriya Nayak (40), a cancer patient from Koelnagar in Rourkela, on Sunday.Head of the department Prof Rabindra Kumar Jena said it is a significant achievement as SCBMCH having all state-of-the-art facilities is the only State-run hospital in the country to complete 50 cases and provide BMT services completely free of cost.

We have a great record of survival rate of patients than other such units elsewhere in the country. Of 50 cases conducted so far, 47 patients are healthy and doing normal activities. Two died due to infection within a month after BMT procedure, another succumbed to brain stroke (not related to BMT or disease) on 178th day, he said.

The BMT unit at SCBMCH has also established a few international and national distinctions. The eldest transplant conducted so far in Asia and Europe region belonged to the unit. Zabar Khan (74), who was suffering from multiple myeloma (a type of blood cancer) is doing fine after the procedure was performed.Similarly, five patients, aged over 65, have been transplanted successfully which is first-of-its-kind in India, Asia and Europe. The first BMT, also known as stem cell transplant, was performed on Sakuntala Sahoo (54) from Kendrapara district on April 23, 2014.

The unit has also mobilised the stem cell adequately in many complicated blood cancer patients who had very low stem cell blood level of 8.7 per micro litre, besides multiple chemotherapy treated cases and successfully performed BMT procedures.

Stating that the priority is being given on adequate stem cell mobilization, collection and engraftment (proper functioning of new bone marrow graft), Prof Jena said the unit is going to start allogenic BMT soon.

We have been doing autologous transplants so far. Our next plan is to start allogenic transplants. We are poised to take complicated cancer patients for BMT. Besides, plans are afoot to expand the unit to a 20-room ward to accommodate huge waiting lists patients, including thalassemia, sickle sell disease and various cancer patients, he added.

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Bone marrow transplant on record run in SCB Medical College and Hospital at Cuttack – The New Indian Express

Irish researcher bags 150000 to make 3D-printed knee implant – Siliconrepublic.com

Irish researcher Prof Daniel Kelly has secured 150,000 in funding to develop a novel implant for treating cartilage damage.

As a recipient of one of the European Research Councils Proof of Concept grants, Prof Daniel Kelly will now spend the next 18 months developing his 3D-printed project entitled Anchor.

Using the 150,000, Kelly will look to develop and commercialise his new medicinal product for cartilage regeneration, employing a postdoctoral researcher to help.

Those active in many sports would be familiar with cartilage damage as a result of injury, of which many cases occur in the knee joint. If left untreated, it can lead to difficulties such as osteoarthritis (OA).

OA can be a debilitating condition, with 80pc of those over the age of 60 experiencing limitations in movement and 25pc saying they cannot perform their major daily activities, according to the World Health Organisation.

Kellys product uses 3D-printed, biodegradable polymer components to make a scaffold, which acts as a template to guide the growth of new tissue by recruiting endogenous bone marrow derived from stem cells.

This, Kelly believes, gives it a competitive edge over similar implants, as standard ones are designed with a finite lifespan, making them unsuitable for younger patients with OA.

Kelly, a principal investigator at AMBER the Trinity College Dublin materials science research centre explained why it could be a major breakthrough for other conditions, such as arthritis.

Our 3D-printed polymer posts will anchor the implant into the bone and will be porous to stimulate the migration of stem cells from the bone marrow into the body of the scaffold, he said.

While various scaffolds like this have been available for some time, they have had limited success, partly because scaffolds need to be anchored securely due to the high forces experienced within the joint. Our 3D-printed posts overcome this problem.

Prior to Anchor, Kelly had worked on this technology in previous projects, such as the ERC-funded StemRepair project to develop a range of porous cartilage-derived scaffolds, and JointPrint.

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Irish researcher bags 150000 to make 3D-printed knee implant – Siliconrepublic.com

SCB conducts 50th bone marrow transplant – Times of India

CUTTACK: The bone marrow transplant unit of SCB Medical College and Hospital achieved a feat on Sunday by successfully conducting its 50th bone marrow transplant (BMT)surgery.

The 50th patient to be operated on Sunday was Bishnupriya Nayak, 40, a cancer patient from Rourkela in Sundargarh district.

The BMT wing was started at SCB in 2014 and in three years the department has operated 50 patients. Besides, it has managed to conduct BMT surgery on a 74-year-old patient Zabar Khan. Hospital authorities claimed that he is the oldest person to undergo bone marrow transplant in the country. “Zabar Khan, a patient of multiple myeloma, was operated in 2015 and he is doing fine. He is the oldest patient to undergo BMT in Asia. Adding to it, we have done BMT on five patients who are above 65 years of age. In elderly patients, the risk factor is quite high,” said head of the BMT unit, Dr R K Jena.

Jena highlighted that so far only three patients out of the 50 have died. “Two patients died due to infection while one succumbed to brain stroke,” added Jena.

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SCB conducts 50th bone marrow transplant – Times of India

Regulating Bone Marrow Protein can Improve Stem Cell Transplants – CMFE News (press release) (blog)

A recent study has identified a key protein capable of regulating the process of new blood cells, including immune cells, which can potentially improve bone and stem cell transplants for donors as well as recipients. The researchers at Technical University of Dresden, Germany, led by the University of Pennsylvania, USA, found that a protein known as Del-1 occupies a key role in the process of hematopoiesis. In addition, researchers inferred that the protein regulator may be modulated to act as potential drug targets in patients affected by certain blood cancers types.

The findings were reported this week (August 28 September 1, 2017) in The Journal of Clinical Investigation.

Del-1 Expression in Hematopoetic Malignancy Key to Boost Myelopoesis in Bone Marrow Transplants

Initially, some of the researchers discovered that Del-1 was the soluble protein that acted as a powerful drug target in gum diseases. Further investigating the role of the protein in hematopoetic malignancy, they inferred that it played a more global role by establishing its expression in a variety of cell types in bone marrow, most notable of them being endothelial cells, CAR cells, and osteoblasts.

The scientists observed that hematopoietic stem cells plays an increasingly important role in various stressful conditions such as bone marrow injury, stem cell transplantation, or systemic infection. These cells affect the production of myeloid cells that forms the core of bone marrow transplants.

Modulating Protein Regulator may Prove Promising in Some Chemotherapies

The team found that the presence of Del-1 in recipient bone marrow facilitated the process of engrafting in recipients by greatly influencing myelopoesis and consequently boosting the formation of new blood cells. The results were observed in experiments conducted in mice suffering with systemic infection. Whereas, in donors, limiting the interaction between the protein and hematopoetic stem cells could boost donor cell numbers in the blood stream, inferred scientists.

Furthermore, the research team observed that the protein regulator also boosts the production of immune-related blood cells. Thus, this may prove to benefit patients suffering with febrile neutropenia who are undergoing chemotherapy.

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Regulating Bone Marrow Protein can Improve Stem Cell Transplants – CMFE News (press release) (blog)

Our Community: Firm pitches in for Woodwynn Farms – Times Colonist

An event-rental business haspartnered with a therapeutic community to introduce altruism into its business model, producing a new kind of accountable commerce.

The Wise Co. has announced it will offer a collection of rental furniture designed and produced by the therapeutic community at Woodwynn Farms.

I had often worked with people who were incredibly generous, and wanted to do good for their communities, said Niecia Dunn, CEO and founder. But due to the hastiness of [the] Western lifestyle, [they] lacked the network or ability to source the right target for the resources they had to offer.

People can now support the farm through renting reasonably priced furniture produced by the farms residents.

Half of all rental costs for the lifetime of the products will return to the 193-acre farm to fund the Believe in People program established by social pioneer Richard Leblanc.

The goal of the program is to raise $30,000 what it costs to sponsor a participant to live at the farm for a year.

The unveiling of the first piece of furniture from the new rental partnership line will take place at a four-course Fall Harvest Dinner, hosted by the Greater Victoria Chamber of Commerce, Sept.7 at Woodwynn Farms, 7789West Saanich Rd.

For more information, go to woodwynnfarms.org.

Donating blood saves lives. Last week, a Vancouver Island woman got to celebrate her 55th birthday and to meet the person whose blood donation made it possible.

Ann Radelet was diagnosed with non-Hodgkins lymphoma in 2003 and underwent three years of chemotherapy. By 2006, the cancer had returned and had transformed into a secondary cancer. The only hope left for her was a bone-marrow transplant.

Her doctor suggested they try a stem-cell transplant instead of a marrow transplant.

But they needed a donor.

The doctors look at antigens in the blood, which they rate out of 10. They tested Radelets two siblings, but found only a five-out-of-10 match, which was not good enough. So they went further afield, looking for donors in a worldwide registry.

Just as she was undergoing her seventh round of chemotherapy, Radelet got the news that they found a nine-out-of-10 match, which translates into a 70per cent success rate.

She received the donated stem cells in February 2007.

She has been cancer-free since then.

Donors are protected by privacy regulations. Radelet was told she would have to wait two years before she could inquire about the donor and only if the donor would allow it.

She eventually found out the donor was a woman named Nicole from Duisburg, Germany. The two corresponded and have talked frequently since then.

When Nicole and Radelet spoke for the first time, they said: We are blood sisters, and that name has stuck for the pair.

In August, Nicole and her sister (an eight-out-of-10 match) visited Vancouver Island for their first meeting in person.

We are all so very excited. I cant ever thank her enough, but I will honour her any way I can, said Radelet. I am so grateful for the team at Vancouver General Hospital and the Canadian Blood Services. They save so many lives in more ways than one.

I am forever eternally grateful to Nicki; she donated blood and stem cells and saved my life. Thank you to all the blood donors out there. I needed lots of it during all my chemotherapy.

My family is still whole. My mother still has her daughter, my brothers still have their sister, my children still have their mom, my husband still has his wife, and now I am a grandma to three adorable babies. I am the most fortunate woman in the world.

Canadian Blood Services maintains the OneMatch Stem Cell and Marrow Network. It is responsible for finding and matching volunteer donors to patients who require stem-cell transplants.

For more information on the network, what it entails and how it saves lives, go to blood.ca.

Need2 Suicide Prevention and Education Support is hosting a public gathering to mark World Suicide Prevention Day, Sunday, Sept. 10 in Centennial Square.

This marks the 15th year of the event. The gathering aims to bring awareness to the efforts to prevent deaths by suicide and the devastating effects of suicide.

The gathering is an open forum where everyone can share. Educational information will be available, along with Need2 support staff.

Suicide is difficult to talk about. It is emotionally charged and carries a great deal of associated shame and stigma.

When persons who are feeling suicidal try to talk about their feelings of desperation, hopelessness and alienation, there is often no one who can really hear their pain.

Need2 provides assistance (urgent or general), runs suicide-prevention programs, puts on workshops and provides information.

The event runs 2 to 4 p.m. Sept. 10 in Centennial Square. For more information, go to need2.ca.

Kane Mercer has just completed a cycle tour across Canada in memory of his father and to raise awareness and funds for Victoria Hospice and palliative care.

Like life, long journeys can be challenging and full of unexpected difficulties, said Mercer. But through a positive attitude, support from friendly people and a consistent effort, these hurdles can be overcome.

In honour of the fifth year since his passing, Mercer is keeping the memory of his father alive with this epic cycling tour across Canada called Ride for Rand.

I decided to make this ride in support of Victoria Hospice in acknowledgment of the support they gave my father and my family, he said. Hospice is a chronically underfunded and neglected area, which I feel deserves attention.

Donations fund almost half of Victoria Hospices annual operating costs. Funds enable it to provide the best possible end-of-life care. For more information, or to donate, go to victoriahospice.org.

The Cook Street Village Activity Centre has just published its Fall Program Guide, listing the many fun and interesting events for the entire family.

Cribbage Tournament Everyone is welcome to this social tournament. It costs $5 to join. It runs 1 to 3:30 p.m. on Sept.13.

Welcome Back to Fall New and seasoned friends are invited to learn about new programs, events and activities. Enjoy a Syrian meal, and watch a play about Emily Carr at this family-friendly event.

Tickets are $12 (or $10 for members) and $6 for children. The event runs 12:20 to 2:30 p.m., Sept. 14 Please purchase tickets by Sept. 8.

International Day of Older Persons Celebrate the United Nations International Day of Older Persons with free activities. This event is free to attend. It runs 8:30 a.m. to 4 p.m. Sept. 30.

Other activities taking place at the centre include yoga, Pilates, Tai Chi, learning different languages, workshops, music, art, listening to guest speakers, learning about computers and seasonal events.

Membership includes discounted rates for courses and daily drop-in programs.

Volunteers are always welcome.

All events take place at the Cook Street Village Activity Centre, 380 Cook St.

For more information, go to cookstreetvillageactivitycentre.com.

Seniors Serving Seniors is recruiting volunteers for its Return to Health Program, as well as candidates for its October training session.

Training for volunteers, funded by the United Way of Greater Victoria, consists of a comprehensive course on seniors concerns and services.

Graduates also attend monthly, two-hour support meetings throughout the year.

Return to Health volunteers provide companionship and social support for frail seniors returning home after a hospital stay.

Volunteers visit clients and offer assistance to help them connect to services and regain self-confidence. The goal of the program is to assist clients in finding practical services they might need following hospitalization, re-socializing and making new friends at seniors social programs in the area.

Training includes: Effective communication skills, nutrition, the effects of disease on normal aging, navigating the health-care system, and how to get access to community programs.

Training for new volunteers takes place from 1 to 4 p.m. every Thursday over five weeks beginning on Oct. 19.

Please call the Return to Health education co-ordinator, Donna Ross, at 250-655-1327 to register for the information session on Oct. 12.

For more information, go to seniorsservingseniors.bc.ca.

Deconstructing Comfort, an interdisciplinary arts exhibition presenting the work of seven contemporary Indigenous artists and artists of colour, opens Friday at Open Space.

Artists include Luli Eshraghi, Jamelie Hassan, Syrus Marcus Ware, Lisa Myers, Nadia Myre, Haruko Okano and Philip Kevin Paul.

The exhibition co-curators, Michelle Jacques, Doug Jarvis and France Trpanier, examine: Decolonization and Indigenization; issues raised by Black Lives Matter; calls to action from the Truth and Reconciliation Commission; Islamophobia; unsettling settlers; and Canada 150 celebrations.

Deconstructing Comfort runs to Oct. 14. A public reception will take place on Sept. 25 as part of the public program for the Primary Colours/Couleurs primaires gathering.

This three-year initiative seeks to place Indigenous art practices at the centre of the Canadian art system. It also asserts that art practices by people of colour, which have roots around the world, play a critical role in any discussion that imagines Canadas future.

The initiative includes a major multidisciplinary, trilingual Lekwungen, French and English gathering at the Songhees Wellness Centre, on Lekwungen territories.

For more information, go to primary-colours.ca.

More than a dozen survivors of Japanese-Canadian internment during the Second World War will speak of their experiences at a luncheon commemorating the 75th anniversary of the saga, Sept. 10.

The Victoria Nikkei Cultural Society is hosting the event, which tells the tragedy of the relocation and internment of Japanese-Canadians during the conflict.

Because its so hard to imagine this happening today, its critical that all Canadians whether they have Japanese heritage or not remember what happened with the internments during the Second World War, said Tsugio Kurushima, president of the society. We are fortunate to still have first-hand witnesses who can share their stories with the generations who followed them.

From 1942 until 1949 (four years after the end of the war), Japanese-Canadians living in coastal British Columbia were detained by the government. They were relocated to camps and farms in the Interior and in the rest of Canada, restricted in their movement and stripped of their businesses and homes.

To add insult to injury, the sale of their personal property was used to fund the internments.

People who never committed a crime were treated like criminals simply because of their heritage, said Kurushima. Its a wrong the Canadian government apologized for in 1988, along with the launch of a redress program.

There will also be a presentation by Jordan Stanger-Ross, director of the Landscapes of Injustice project, housed at the University of Victoria.

He will give an update on the project, which explores the forced dispossession of Japanese-Canadians.

The event includes a buffet lunch with two hot entres, including a vegetarian lasagna option.

Tickets are $15 adults, $7.50 for children 5 to 12. The event runs 1 to 4:30 p.m. Sept. 10 at the Ambrosia Event Centre, 638 Fisgard St.

Tickets available from Patti Ayukawa, Real English Victoria, #301 1111 Blanshard St. or 250-858-8445. For more information, go to vncs.ca.

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Our Community: Firm pitches in for Woodwynn Farms – Times Colonist

In Osteoporosis, differentiation of mesenchymal stem cells …

Biol Res 45: 279-287, 2012

RESEARCH ARTICLES

In Osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis

Ana Mara Pino1, Clifford J. Rosen2 and J. Pablo Rodrguez1*

1Laboratorio de Biologa Celular y Molecular, INTA, Universidad de Chile, 2Maine Medical Center Research Institute, Scarborough, Maine, USA.

ABSTRACT

The formation, maintenance, and repair of bone tissue involve close interlinks between two stem cell types housed in the bone marrow: the hematologic stem cell originating osteoclasts and mesenchymal stromal cells (MSCs) generating osteoblasts. In this review, we consider malfunctioning of MSCs as essential for osteoporosis. In osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis and insufficient osteoblastogenesis.

MSCs are the common precursors for both osteoblasts and adipocytes, among other cell types. MSCs’ commitment towards either the osteoblast or adipocyte lineages depends on suitable regulatory factors activating lineage-specific transcriptional regulators. In osteoporosis, the reciprocal balance between the two differentiation pathways is altered, facilitating adipose accretion in bone marrow at the expense of osteoblast formation; suggesting that under this condition MSCs activity and their microenvironment may be disturbed. We summarize research on the properties of MSCs isolated from the bone marrow of control and osteoporotic post-menopausal women. Our observations indicate that intrinsic properties of MSCs are disturbed in osteoporosis. Moreover, we found that the regulatory conditions in the bone marrow fluid of control and osteoporotic patients are significantly different. These conclusions should be relevant for the use of MSCs in therapeutic applications.

Key words: MSCs, osteoporosis, adipogenesis, bone marrow microenvironment

BACKGROUND

The formation, maintenance, and repair of bone tissue depend on fine-tuned interlinks in the activities of cells derived from two stem cell types housed in the bone marrow interstice. A hematologic stem cell originates osteoclasts, whereas osteoblasts derive from mesenchymal stem cells (MSCs). Bone tissue is engaged in an unceasing process of remodelling through the turnover and replacement of the matrix: while osteoblasts deposit new bone matrix, osteoclasts degrade the old one.

Bone marrow provides an environment for maintaining bone homeostasis. The functional relationship among the different cells found in bone marrow generates a distinctive microenvironment via locally produced soluble factors, the extracellular matrix components, and systemic factors (Raisz, 2005; Sambrook and Cooper, 2006), allowing for autocrine, paracrine and endocrine activities. If only the main cellular components of the marrow stroma are considered, the activity of adipocytes, macrophages, fibroblasts, hematopoietic, endothelial and mesenchymal stem cells and their progeny bring about a complex range of signals.

Osteoporosis is a bone disease characterized by both decreased bone quality and mineral density. In postmenopausal osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis, inadequate osteoblastogenesis and altered bone microarchitecture.

The pathogenesis of the disease is hitherto unknown, hence the interest in basic and clinical research on the mechanisms involved (Raisz, 2005; Sambrook and Cooper, 2006). Cell studies on the origin of postmenopausal osteoporosis initially focused on osteoclastic activity and bone resorption processes; then on osteoblastogenesis, and more recently on the differentiation potential of mesenchymal stem cells (MSCs) (Shoback, 2007). Moreover, distinctive environmental bone marrow conditions appear to provide support for the development and maintenance of unbalanced bone formation and resorption (Nuttall and Gimble, 2004; Tontonoz et al., 1994). In this review, we consider the participation of the differentiation potential of MSCs, the activity of bone marrow adipocytes and the generation of a distinctive bone marrow microenvironment.

MESENCHYMAL STEM CELLS (MSCs)

Bone marrow contains stem-like cells that are precursors of nonhematopoietic tissues. These cells were initially referred to as plastic-adherent cells or colony forming-unit fibroblasts and subsequently as either mesenchymal stem cells or marrow stromal cells (MSCs) (Minguell et al., 2001; Lindnera et al., 2010; Kolf et al., 2007). There is much interest in these cells because of their ability to serve as a feeder layer for the growth of hematopoietic stem cells, their multipotentiality for differentiation, and their possible use for both cell and gene therapy (Minguell et al., 2001; Kolf et al., 2007). Friedenstein et al. (1970) initially isolated MSCs by their adherence to tissue culture surfaces, and essentially the same protocol has been used by other investigators. The isolated cells were shown to be multipotential in their ability to differentiate in culture or after implantation in vivo, giving rise to osteoblasts, chondrocytes, adipocytes, and/or myocytes.

MSCs populations in the bone marrow or those that are isolated and maintained in culture are not homogenous, but rather consist of a mixture of uncommitted, partially committed and committed progenitors exhibiting divergent stemness (Baksh et al., 2004). These heterogeneous precursor cells are morphologically similar to the multipotent mesenchymal stem cells, but differ in their gene transcription range (Baksh et al., 2004). It has been proposed that in such populations, cell proliferation, differentiation and maturation are in principle independent; stem cells divide without maturation, while cells close to functional competence may mature, but do not divide (Song et al., 2006).

Several molecular markers identify committed progenitors and the end-stage phenotypes, but at present there are no reliable cell markers to identify the uncommitted mesenchymal stem cells. Given the difficulty to identify a single marker to evaluate the population of stem cells, various combinations of these markers may be used (Seo et al., 2004; Lin et al., 2008; Xu et al., 2009). Therefore, MSCs are mainly defined in terms of their functional capabilities: self-renewal, multipotential differentiation and transdifferentiation (Baksh et al., 2004).

Hypothetically, the fate of MSCs appears to be determined during very early stages of cell differentiation (“commitment”). During this mostly unknown period, both intrinsic (genetic) and environmental (local and/or systemic) conditions interplay to outline the cell’s fate towards one of the possible lineages. Based on microarray assays comparing gene expression at the stem state and throughout differentiation, it has been proposed that MSCs multilineage differentiation involves a selective mode of gene expression (Baksh et al., 2004; Song et al., 2006). It appears that “stemness” is characterized by promiscuous gene expression, where pluripotential differentiation results from the maintenance of thousands of genes at their intermediate expression levels. Upon commitment to one fate, only the few genes that are needed for differentiation towards the target tissue are selected for continuous expression, while the rest are downregulated (Zipori, 2005; Zipori, 2006).

The gene expression profile of undifferentiated human MSCs (h-MSCs) show high expression of several genes (Song et al., 2006; Tremain et al., 2001), but the contribution of such genes in preserving h-MSC properties, such as self-renewal and multilineage differentiation potential, or in regulating essential signalling pathways is largely unknown (Song et al., 2006). Several factors like age (Zhou et al., 2008), culture condition (Kultere et al., 2007), microenvironment (Kuhn and Tuan, 2010), mechanical strain (McBride et al., 2008) and some pathologies (Seebach et al., 2007; Hofer et al., 2010) appear to affect MSCs’ intrinsic activity.

MSCs’ commitment towards either the osteoblast or adipocyte lineage is determined by a combination of regulatory factors in the cells’ microenvironment. The adequate combination leads to the activation of lineage-specific transcriptional regulators, including Runx2, Dlx5, and osterix for osteoblasts, and PPARy2 and a family of CAAT enhancer binding proteins for adipocytes (Murunganandan et al., 2009). Although the appropriate collection of regulatory factors required for suitable differentiation of MSCs is largely unknown, the TGF/BMPs, Wnt and IGF-I signals are briefly considered.

Several components of the BMP family are secreted in the MSCs’ microenvironment (Lou et al., 1999, Gori et al., 1999; Gimble et al., 1995); BMP-2/4/6/7 have been identified as mediators for MSCs differentiation into osteoblasts or adipocytes (Muruganadan et al., 2009). The intracellular effects of BMPs are mediated by an interaction with cell surface BMP receptors (BMPRs type I and type II) (Gimble et al., 1995). It seems that differentiation into adipocytes or osteoblasts is highly dependent on the type of receptor I expressed by the cells, so that adipogenic differentiation requires signaling through BMPR IA, while osteogenic differentiation is dependent on BMPR IB activation (Gimble et al., 1995). The active receptors trigger the activation of Smad proteins, which induce specific genes. Under osteogenic differentiation, BMP action promotes osterix formation through Runx2-dependent and Runx2-independent pathways, thereby triggering osteogenic differentiation (Gori et al., 1999; Shapiro, 1999).

In addition to the role of BMPs in bone formation, BMPs also positively mediate the adipogenic differentiation pathways (Haiyan et al., 2009). It has been demonstrated that there is a binding site for Smad proteins in the promoter region of PPARy2 (Lecka-Czernik et al., 1999), and over-expression of Smad2 protein suppresses the expression of Runx2 (Li et al., 1998). These observations suggest that adequate content of osteoblasts and adipocytes in the bone marrow is dependent on balanced signaling through this pathway. Moreover, considering the distinct role assigned to BMPRIA and BMPRIB, the temporal gain or loss of a subtype of BMP receptors by MSCs could be critical for commitment and subsequent differentiation (Gimble et al., 1995144).

Wnt signaling in MSCs is also decisive for the reciprocal relationship among the osteo/adipogenic pathways. Activation of the Wnt/p-catenin pathway directs MSCs differentiation towards osteoblasts instead of adipocytes (Bennett et al., 2005; Ross et al., 2000; Moldes et al., 2003). Animal studies have shown that activation of the Wnt signaling pathway increases bone mass, preventing both hormone-dependent and age-induced bone loss (Bennett et al., 2005). Furthermore, Wnt activation may control cell commitment towards osteoblasts by blocking adipogenesis through the inhibition of the expression of both C/EBP and PPARy adipogenic transcription factors, as demonstrated in vivo in humans (Qiu et al., 2007), in transgenic mice expressing Wnt 10b (Bennett et al., 2005) and in vitro (Rawadi et al., 2003). MSCs’ self-renewing and maintenance of the undifferentiated state appear to be dependent on appropriate canonical Wnt signaling, promoting increased proliferation and decreased apoptosis (Boland et al., 2004; Cho et al., 2006). The overexpression of LRP5, an essential co-receptor specifically involved in canonical Wnt signaling, has been reported to increase proliferation of MSCs (Krishnan et al., 2006). In addition, disruption in vivo or in vitro of -catenin signaling promoted spontaneous conversion of various cell types into adipocytes (Bennett et al., 2002). Moreover, the importance of this pathway for bone mineral density has been highlighted by the observation that genetic variations at either the LRP5 or Wnt10b gene locus are associated with osteoporosis (Brixen et al., 2007; Usui et al., 2007).

Also, insulin-like growth factor-I (IGF-I) signalling is clearly an important factor in skeletal development. The IGF regulatory system consists of IGFs (IGF-I and IGF-II), Type I and Type II IGF receptors, and regulatory proteins including IGF-binding proteins (IGFBP-1-6) and the acid-labile subunit (ALS) (Rosen et al., 1994). The ligands in this system (i.e. IGFs) are potent mitogens, and in some circumstances differentiation factors, that are bound in the circulation and interstitial fluid as binary (to IGFBPs) or ternary complexes (IGF-ALS-IGFBP-3 or -5) with little free IGF-I or -II. IGF bio-availability is regulated by the interaction of these molecules at the receptor level; hence changes in any component of the system will have profound effects on the biologic activity of the ligand. The IGFBPs have a particularly important role in regulating IGF-I access to its receptor, since their binding affinity exceeds that of the IGF receptors. The IGF system is unique because the IGFBPs are regulated in a cell-specific manner at the pericellular microenvironment, such that small changes in their concentrations could strongly influence the mitogenic activity of IGF-I (Jones and Clemmons, 1995; Hwa and Rosenfeld, 1999; Firth and Baxter, 2002). IGFs are expressed virtually by all tissues, and circulate in high concentrations. Although nearly 80% of the circulating IGF-I comes from hepatic sources, both bone and fat synthesize IGF-I and these tissues contribute to the total circulating pool. Locally produced IGF-I predominates over circulating IGF-I in maintaining skeletal integrity (Rosen et al., 1994; Kawai and Rosen, 2010), and both ALS and IGFBP-3 participate in regulating bone function. However, the possible autocrine/paracrine roles of IGF-I and IGFBPs in marrow (Liu et al., 1993; Peng et al., 2003) or in osteoblast (Zhao et al., 2000; Zhang et al., 2002; Wang et al., 2007) are practically unknown.

RELATIONSHIP BETWEEN THE OSTEO- / ADIPOGENESIS PROCESSES – THE FAT THEORY FOR OSTEOPOROSIS

Since in the bone marrow MSCs are the common precursor cells for osteoblast and adipocytes, adequate osteoblast formation requires diminished adipogenesis. As pointed out above, MSCs commitment and differentiation into a specific phenotype depends on hormonal and local factors (paracrine/autocrine) regulating the expression and/or activity of master differentiation genes (Nuttall and Gimble, 2004; Muruganadan et al., 2009) (Figure 1). A reciprocal relationship has been postulated to exist between the two differentiation pathways whose alteration would facilitate adipose accretion in the bone marrow, at the expense of osteoblast formation, thus decreasing bone mass (Reviewed in Rosen et, al 2009; Rodrguez et al.. 2008; Rosen and Bouxtein, 2006). Such unbalanced conditions prevail in the bone marrow of osteoporosis patients, upsetting MSC activity and the microenvironment (Nuttall and Gimble, 2004; Moerman et al., 2004; Rosen and Bouxtein, 2006). This proposition is known as the fat theory for osteoporosis. Moreover, this alteration of osteo-/adipogenic processes is also observed in other conditions characterized by bone loss, such as aging, immobilization, microgravity, ovariectomy, diabetes, and glucocorticoid or tiazolidindione treatments, highlighting the harmful consequence of marrow adipogenesis in osteogenic disorders (Wronski et al., 1986; Moerman et al., 2004; Zayzafon et al., 2004; Forsen et al., 1999).

Cell studies comparing the differentiation potential of MSCs derived from osteoporotic patients (o-MSCs) with that of control MSCs (c-MSCs) have shown unbalanced osteogenic/adipogenic processes, including increased adipose cell formation, counterbalanced by reduced production of osteogenic cells (Nuttall and Gimble, 2004; Rodrguez et al., 2008; Rosen and Bouxtein, 2006). Further research on MSC differentiation has shown that activation of PPARy2, a master transcription factor of adipogenic differentiation, positively regulates adipocyte differentiation while acting as a dominant negative regulator of osteogenic differentiation (Lecka-Czernik et al., 1999; Jeon et al., 2003; Khan and Abu-Amer, 2003). In contrast, an increase in bone mass density was observed in a PPARy deficient mice model; even the heterozygous deficient animals showed high bone mass and increased osteoblastogenesis (Cock et al., 2004). On the other hand, Runx2 expression by MSCs inhibits their differentiation into adipocytes, as may be concluded from experiments in Runx2-/- calvarial cells, which spontaneously differentiate into adipocytes (Kobayashi et al., 2000).

In vivo observations further support the fat theory. Early studies observed that osteoporosis was strongly associated with bone marrow adipogenesis. Iliac crest biopsies showed that bone marrow from osteoporotic patients had a considerable accumulation of adipocytes in relation to that of healthy elderly women (Moerman et al., 2004; Meunier et al., 1971). More recently, increased bone marrow adiposity measured by in vivo proton magnetic resonance (1H-MRS) has been associated with decreased bone mineral density in patients with low bone density (Griffith et al., 2005; Yeung et al., 2005; Blake et al., 2008).

In newborn mammals there is no marrow fat; however the number of adipocytes increases with age such that in humans over 30 years of age, most of the femoral cavity is occupied by adipose tissue (Moore and Dawson, 1990). The function of marrow fat is largely unknown; in humans it was first considered to be ‘filler’ for the void left by trabecular bone during aging or after radiation. Later, these cells have been proposed to have a role as an energy source, or as modulators of adjacent tissue by the production of paracrine, and autocrine factors (reviewed in Rosen et al., 2009). In fact, adipokines, steroids, and cytokines (Lee et al., 2002; Pino et al., 2010; Rosen et al., 2009;) can exert profound effects on neighboring marrow cells, sustaining or suppressing hematopoietic and osteogenic processes (Omatsu et al., 2010; Krings et al., 2012; Rosen et al., 2009; Rodrguez et al., 2008).

Thus, the function of bone marrow adipose tissue may be similar to that of extra medullary fat. As such, it has been well established that unbalanced production of signaling products from subcutaneous or visceral fat modulates several human conditions including obesity, lipodystrophy, atherogenesis, diabetes and inflammation. Recent studies in mice, suggest a complex fat phenotype in the bone marrow, presenting mixed brown and white adipose properties (Lecka-Czernik, 2012). Further work is needed to find out whether differences in the quality or quantity of marrow fat, take part in deregulated bone remodelling in some bone diseases.

STUDIES ON THE ACTIVITY OF OSTEOPOROTIC MSCs

Because of their ability to self-renew, human MSCs can be expanded and differentiated in vitro, offering many perspectives for tissue engineering and regenerative medicine approaches. However, there is scarce information on whether specific diseases affect the properties of MSCs, because of the difficult accessibility to human bone marrow in health and disease (Cipriani et al., 2011; Corey et al., 2007).

Our research has focused on the properties of MSCs isolated from bone marrow of control and osteoporotic post-menopausal women. We grouped our observations on functional characteristics of o-MSCs and c- MSCs in three categories, which are summarized in Table I, as follows:

General activities: h-MSCs isolated from osteoporotic and control donors have similar CFU-F, but different proliferation rates. O-MSCs showed significantly diminished proliferation rate and decreased mitogenic response to IGF-I. The pERK/ERK ratio is increased in o-MSCs, compared with control c-MSCs. In other cell types, activation of the MEK/ERK signalling pathway enhances the activity of adipogenic transcription factors (Prusty et al., 2002). We also observed decreased TGF- production by o-MSCs, as well as decreased capacity to generate and maintain a type I collagen-rich extracellular matrix, both conditions supporting cell differentiation into the adipocyte phenotype. Then, considering that the lineage fate of MSCs is dependent on early activation by specific BMPs, PPARy and Wnt signaling (Ross et al., 2000; Rawadi et al., 2003; Westendorf et al., 2004; Baron and Rawadi, 2007), we compared the expression level of some genes related to these pathways in c- and o- MSCs. Results obtained by RT-PCR showed that in c- and o-MSCs the expression level of mRNA for -catenin, Dkk-1, and BMPRIB was similar; while the level of mRNA for Wnt 3a was undetectable in both types of samples. The expression level of mRNA for GSK-3p, LRP6 and Osx was lower in o-MSCs than in c-MSCs, while the mRNA level for Ror2, Wnt 5a, BMPRIA showed doubtful. To further quantify the expression level of GSK-3P, LRP6, Osx, Ror2, Wnt 5a, BMPRIA real time RT-PCR was performed. As shown in Table I, statistically significant decreased mRNA levels for GSK-3p, LRP6 and Osx (0.64, 0.26 and 0.18 fold, respectively) were observed in o-MSCs, as compared to c-MSCs. In addition, mRNA levels for Ror2, Wnt 5a, and BMPRIA were similar in both types of cell samples.

These data suggest impaired regulation by the BMPs and Wnt pathways in o-MSCs, representing some intrinsic deviation from control cells that might underlie the impaired self-renewal, and adipogenic/osteogenic differentiation potential observed in o-MSCs. mRNA levels for Ror2, Wnt 5a, and BMPRIA were similar in both types of cell samples.

STUDIES ON THE ACTIVITY OF BONE MARROW FLUID OF POST-MENOPAUSAL WOMEN

Distinctive environmental bone marrow conditions appear to support the development and maintenance of the balance between bone resorption and bone formation. Knowledge is scarce about the intramedullar concentration of compounds with recognized regulatory effects on bone formation or resorption and is limited to some pathologic conditions or estimated from measurements in plasma (Wiig et al., 2004; Iversen and Wiig, 2005; Lee et al., 2002; Khosla et al., 1994).

Measurement of soluble molecules found in human bone marrow has been particularly difficult, not only because of tissue seclusion, but also because of the complicated anatomy and blood perfusion of bone. Since it may be expected that concentrations measured in the bone marrow fluid (BMF) more reliably reflect the physiologically relevant levels in the interstitial compartment surrounding the bone cells than values found in blood, we isolated the extracellular bone marrow fluid by directly spinning bone marrow samples for 20 min at 900xg. Considering the complex organization in such a regulatory milieu, we opted for evaluating some molecules recognized as markers of adipocyte, proinflammatory or osteoclastic/osteoblastic activity (Pino et al., 2010).

The concentrations of cytokines or receptors measured in the bone marrow extracellular fluid from control and osteoporotic human donors are indicated in Table II. In addition, the concentrations of IGF-I and its IGFBPs were analyzed, as well as the C-terminal telopeptide cross-links of type I collagen (CTX). Results summarized in Table II indicate significantly different concentrations of regulatory molecules in the extracellular fluid of control versus osteoporotic women; this last group was characterized by higher content of proinflammatory and adipogenic cytokines. Also, osteoporotic samples showed decreased leptin bioavailability, suggesting that insufficient leptin action may characterize the osteoporotic bone marrow (Pino et al., 2010). In addition, bioavailability of IGF-I appears diminished in o-BMF, as shown by the increased IGFBP3/IGF-I ratio.

TABLE II

Regulatory activity in bone marrow fluid of post-menopausal women

Taken together our results and those of other researchers identify significant differences between functional properties of control and osteoporotic MSCs, displayed in vitro, in cells under basal or differentiating conditions. Moreover, it can be concluded that such divergence prevails also in vivo, because the bone marrow fluid of osteoporotic patients characterizes by unfavourable content of several regulatory molecules. Therefore, the properties of both MSCs and bone marrow microenvironment are significantly impaired in osteoporotic patients, negatively affecting bone formation.

CONCLUSIONS

In the pathogenesis of osteoporosis, impairment of both MSCs functionality and microenvironment add to the known detrimental effect of increased osteoclast activity, resulting in decreased bone formation.

O-MSCs are characterized by intrinsic functional alteration leading to poor osteogenic capability and increased adipogenesis. Osteoporotic bone marrow microenvironment differs from the control microenvironment by increased concentration of pro-adipogenic and pro-inflammatory regulatory factors.

The content and/or quality of adipocytes in the bone marrow appear critical to delineate impairing of MSCs; in this sense osteoporosis could be homologated to other age-related diseases such as obesity, atherogenesis and diabetes, which are characterized by extramedullar unbalanced adipocyte formation and signaling.

Currently it is not known how damaged o-MSCs emerge, further work is needed to ascertain the role of the microenvironment, and genetic and epigenetic factors, as proposed for other stem cells-related pathologies.

The conclusion that intrinsic properties of MSCs are altered in osteoporosis should be relevant for the therapeutic use of MSCs, which represent an interesting promise for regenerative medicine for several severe human diseases.

The possibility of reversing o-MSCs impairment opens new perspectives for osteoporosis therapy.

ACKNOWLEDGEMENTS

We thank Dr. Mariana Cifuentes for her critical review of the manuscript and valuable comments. This work was supported by a grant from the Fondo Nacional de Ciencia y Tecnologa (FONDECYT # 1090093)

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In Osteoporosis, differentiation of mesenchymal stem cells …

Dr Con Man: the rise and fall of a celebrity scientist who fooled almost everyone – The Guardian

Scientific pioneer, superstar surgeon, miracle worker thats how Paolo Macchiarini was known for several years. Dressed in a white lab coat or in surgical scrubs, with his broad, handsome face and easy charm, he certainly looked the part. And fooled almost everyone.

Macchiarini shot to prominence back in 2008, when he created a new airway for Claudia Castillo, a young woman from Barcelona. He did this by chemically stripping away the cells of a windpipe taken from a deceased donor; he then seeded the bare scaffold with stem cells taken from Castillos own bone marrow. Castillo was soon back home, chasing after her kids. According to Macchiarini and his colleagues, her artificial organ was well on the way to looking and functioning liked a natural one. And because it was built from Castillos own cells, she didnt need to be on any risky immunosuppressant drugs.

This was Macchiarinis first big success. Countless news stories declared it a medical breakthrough. A life-saver and a game-changer. We now know that wasnt true. However, the serious complications that Castillo suffered were, for a long time, kept very quiet.

Meanwhile, Macchiarinis career soared. By 2011, he was working in Sweden at one of the worlds most prestigious medical universities, the Karolinska Institute, whose professors annually select the winner of the Nobel prize in physiology or medicine. There he reinvented his technique. Instead of stripping the cells from donor windpipes, Macchiarini had plastic scaffolds made to order. The first person to receive one of these was Andemariam Beyene, an Eritrean doctoral student in geology at the University of Iceland. His recovery put Macchiarini on the front page of the New York Times.

Macchiarini was turning the dream of regenerative medicine into a reality. This is how NBCs Meredith Vieira put it in her documentary about Macchiarini, appropriately called A Leap of Faith: Just imagine a world where any injured or diseased organ or body part you have is simply replaced by a new artificial one, literally manmade in the lab, just for you. This marvelous world was now within reach, thanks to Macchiarini.

Last year, however, the dream soured, exposing an ugly reality.

Macchiarini gave his regenerating windpipes to 17 or more patients worldwide. Most, including Andemariam Beyene, are now dead. Those few patients who are still alive including Castillo have survived in spite of the artificial windpipes they received.

In January 2016, Macchiarini received an extraordinary double dose of bad press. The first was a Vanity Fair article about his affair with Benita Alexander, an award-winning producer for NBC News. She met Macchiarini while producing A Leap of Faith and was soon breaking one of the cardinal rules of journalism: dont fall in love with the subject of your story.

By the time the program aired, in mid-2014, the couple were planning their marriage. It would be a star-studded event. Macchiarini had often boasted to Alexander of his famous friends. Now they were on the wedding guest list: the Obamas, the Clintons, Vladimir Putin, Nicolas Sarkozy and other world leaders. Andrea Bocelli was to sing at the ceremony. None other than Pope Francis would officiate, and his papal palace in Castel Gandolfo would serve as the venue. Thats what Macchiarini told his fiancee.

But as the big day approached, Alexander saw these plans unravel, and finally realised that her lover had lied about almost everything. The pope, the palace, the world leaders, the famous tenor they were all fantasies.

Likewise the whole idea of a wedding: Macchiarini was still married to his wife of 30 years.

Macchiarinis deceit was so outlandish, Vanity Fair sought the opinion of the Harvard professor Ronald Schouten, an expert on psychopaths, who gave this diagnosis-at-a-distance: Macchiarini is the extreme form of a con man. Hes clearly bright and has accomplishments, but he cant contain himself. Theres a void in his personality that he seems to want to fill by conning more and more people.

Which left a big, burning question in the air: if Macchiarini was a pathological liar in matters of love, what about his medical research? Was he conning his patients, his colleagues and the scientific community?

The answer came only a couple of weeks later, when Swedish television began broadcasting a three-part expos of Macchiarini and his work.

Called Experimenten (The Experiments), it argued convincingly that Macchiarinis artificial windpipes were not the life-saving wonders wed all been led to believe. On the contrary, they seemed to do more harm than good something that Macchiarini had for years concealed or downplayed in his scientific articles, press releases and interviews.

Faced with this public relations disaster, the Karolinska Institute immediately promised to investigate the allegations but then, within days, suddenly announced that Macchiarinis contract would not be extended.

Macchiarinis fall was swift, but troubling questions remain about why he was allowed to continue his experiments for so long. Some answers have emerged from the official inquiries into the Karolinska Institute and the Karolinska University hospital. They identified many problems with the way the twin organisations handled him.

Macchiarinis fame had won him well-placed backers. These included Harriet Wallberg, who was the vice-chancellor of the Karolinska Institute in 2010, when Macchiarini was recruited. She pushed through his appointment despite the fact that he had some very negative references and dubious claims on his rsum.

This set a dangerous example. It showed department heads and colleagues that they should give Macchiarini special treatment.

He could do pretty much as he pleased. In the first couple of years at Karolinska, he put plastic airways into three patients. Since this was radically new, Macchiarini and his colleagues should have tested it on animals first. They didnt.

Likewise, they didnt undertake a proper risk assessment of the procedure, nor did Macchiarinis team seek government permits for the plastic windpipes, stem cells, and chemical growth factors they used. They didnt even seek the approval of Stockholms ethical review board, which is based at Karolinska.

Though Macchiarini was in the public eye, he was able to sidestep the usual rules and regulations. Or rather, his celebrity status helped him do so. Karolinskas leadership expected big things from their superstar, things that would bring prestige and funding to the institute.

They also cited a loophole known as compassionate use. Macchiarini, they claimed, wasnt really doing clinical research. No, he was just caring for his patients who were, one and all, facing certain death with no other treatment options available and no time to waste. In such dire circumstances, new treatments can be tried as a last resort.

This argument didnt wash with those who later investigated the case. In their view, Macchiarini was certainly engaged in clinical research. Besides which, compassionate concerns dont override the basic principles of patient safety and informed consent. Macchiarini, meanwhile, said he did not accept the findings of the disciplinary board.

As it turned out, Macchiarinis patients werent all at deaths door at the time he treated them. Andemariam Beyene, for instance, had recurrent cancer of the windpipe but, aside from a cough, was still in good health. But even if his days had been numbered, this didnt necessarily justify what Macchiarini put him through.

Beyenes death two and a half years after the operation, caused by the failure of his artificial airway, was a grueling ordeal. According to Pierre Delaere, a professor of respiratory surgery at KU Leuven, Belgium, Macchiarinis experiments were bound to end badly. As he said in Experimenten: If I had the option of a synthetic trachea or a firing squad, Id choose the last option because it would be the least painful form of execution.

Delaere was one of the earliest and harshest critics of Macchiarinis engineered airways. Reports of their success always seemed like hot air to him. He could see no real evidence that the windpipe scaffolds were becoming living, functioning airways in which case, they were destined to fail. The only question was how long it would take weeks, months or a few years.

Delaeres damning criticisms appeared in major medical journals, including the Lancet, but werent taken seriously by Karolinskas leadership. Nor did they impress the institutes ethics council when Delaere lodged a formal complaint.

Support for Macchiarini remained strong, even as his patients began to die. In part, this is because the field of windpipe repair is a niche area. Few people at Karolinska, especially among those in power, knew enough about it to appreciate Delaeres claims. Also, in such a highly competitive environment, people are keen to show allegiance to their superiors and wary of criticising them. The official report into the matter dubbed this the bandwagon effect.

With Macchiarinis exploits endorsed by management and breathlessly reported in the media, it was all too easy to jump on that bandwagon.

And difficult to jump off. In early 2014, four Karolinska doctors defied the reigning culture of silence by complaining about Macchiarini. In their view, he was grossly misrepresenting his results and the health of his patients. An independent investigator agreed. But the vice-chancellor of Karolinska Institute, Anders Hamsten, wasnt bound by this judgement. He officially cleared Macchiarini of scientific misconduct, allowing merely that hed sometimes acted without due care.

For their efforts, the whistleblowers were punished. When Macchiarini accused one of them, Karl-Henrik Grinnemo, of stealing his work in a grant application, Hamsten found him guilty. As Grinnemo recalls, it nearly destroyed his career: I didnt receive any new grants. No one wanted to collaborate with me. We were doing good research, but it didnt matter I thought I was going to lose my lab, my staff everything.

This went on for three years until, just recently, Grinnemo was cleared of all wrongdoing.

The Macchiarini scandal claimed many of his powerful friends. The vice-chancellor, Anders Hamsten, resigned. So did Karolinskas dean of research. Likewise the secretary-general of the Nobel Committee. The university board was dismissed and even Harriet Wallberg, whod moved on to become the chancellor for all Swedish universities, lost her job.

Unfortunately, the scandal is much bigger than Karolinska, which accounts for only three of the patients who have received Macchiarinis regenerating windpipes.

The other patients were treated at hospitals in Barcelona, Florence, London, Moscow, Krasnodar, Chicago and Peoria. None of these institutions have faced the same kind of public scrutiny. None have been forced to hold full and independent inquiries. They should be.

If the sins of Karolinska have been committed elsewhere, it is partly because medical research facilities share a common milieu, which harbours common dangers. One of these is the hype surrounding stem cells.

Stem cell research is a hot field of science and, according to statistics, also a rather scandal-prone one. Articles in this area are retracted 2.4 times more often than the average for biomedicine, and over half of these retractions are due to fraud.

Does the heat of stem cell research the high levels of funding, prestige and media coverage it enjoys somehow encourage fraud? Thats what our experience of medical research leads us to suspect. While there isnt enough data to actually prove this, we do have some key indicators.

We have, for example, a growing list of scientific celebrities who have committed major stem cell fraud. There is South Koreas Hwang Woo-suk who, in 2004, falsely claimed to have created the first human embryonic stem cells by means of cloning. A few years ago, Japans Haruko Obokata pulled a similar con when she announced to the world a new and simple and fake method of turning ordinary body cells into stem cells.

Hwang, Obokata and Macchiarini were all attracted to the hottest regions of stem cell research, where hope for a medical breakthrough was greatest. In Macchiarinis case, the hope was that patients could be treated with stem cells taken from their own bone marrow.

Over the years, this possibility has generated great excitement and a huge amount of research. Yet, for the vast majority of such treatments, there is little solid evidence that they work. (The big exception is blood stem cell transplantation, which has been saving the lives of people with leukemia and other cancers of the blood for decades.)

Its enough to worry officials from the US Food and Drug Administration (FDA). They recently published an article in the New England Journal of Medicine admitting that stem cell research has mostly failed to live up to its therapeutic promise.

An alarmingly wide gap has grown between what we expect from stem cells and what they deliver. Each new scientific discovery brings a flood of stories about how it will revolutionise medicine one day soon. But that day is always postponed.

An unhappy result of this is the rise of pseudo-scientific therapies. Stem cell clinics have sprung up like weeds, offering to treat just about any ailment you can name. In place of clinical data, there are gushing testimonials. There are also plenty of desperate patients who believe because theyve been told countless times that stem cells are the cure, and who cannot wait any longer for mainstream medicine. They and their loved ones fall victim to false hope.

Scientists can also suffer from false hope. To some extent, they believed Macchiarini because he told them what they wanted to hear. You can see this in the speed with which his breakthroughs were accepted. Only four months after Macchiarini operated on Claudia Castillo, his results provisional but very positive were published online by the Lancet. Thereafter it was all over the news.

The popular press also has a lot to answer for. Its love of human interest stories makes it sympathetic to unproven therapies. As studies have shown, the media often casts a positive light on stem cell tourism, suggesting that the treatments are effective and the risks low. It did much the same for Macchiarinis windpipe replacements. A good example is the NBC documentary A Leap of Faith. Its fascinating to rewatch as a lesson on how not to report on medical science.

It is fitting that Macchiarinis career unravelled at the Karolinska Institute. As the home of the Nobel prize in physiology or medicine, one of its ambitions is to create scientific celebrities. Every year, it gives science a show-business makeover, picking out from the mass of medical researchers those individuals deserving of superstardom. The idea is that scientific progress is driven by the genius of a few.

Its a problematic idea with unfortunate side effects. A genius is a revolutionary by definition, a risk-taker and a law-breaker. Wasnt something of this idea behind the special treatment Karolinska gave Macchiarini? Surely, he got away with so much because he was considered an exception to the rules with more than a whiff of the Nobel about him. At any rate, some of his most powerful friends were themselves Nobel judges until, with his fall from grace, they fell too.

If there is a moral to this tale, its that we need to be wary of medical messiahs with their promises of salvation.

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Dr Con Man: the rise and fall of a celebrity scientist who fooled almost everyone – The Guardian

Bone marrow transplant – Doctor NDTV

Wed,17 Dec 2003 05:30:00

Bone marrow transplant is a procedure in which healthy bone marrow is transplanted into a patient whose bone marrow is not functioning properly. Problems in bone marrow are often caused by chemotherapy or radiation treatment for cancer. This procedure can also be done to correct hereditary blood diseases. The healthy bone marrow may be taken from the patient prior to chemotherapy or radiation treatment (autograft), or it may be taken from a donor (allograft).

Wed,17 Dec 2003 05:30:00

Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells called stem cells that produce blood cells. There are three types of blood cells: white blood cells, which fight infection; red blood cells, which carry oxygen to and from organs and tissues; and platelets, which enable the blood to clot.

Wed,17 Dec 2003 05:30:00

Alternatively, hereditary or acquired disorders may cause abnormal blood cell production. In these cases, transplantation of healthy bone marrow may save a patient’s life. Transplanted bone marrow will restore production of white blood cells, red blood cells, and platelets.

Wed,17 Dec 2003 05:30:00

Donated bone marrow must match the patient’s tissue type. It can be taken from the patient, a living relative (usually a brother or a sister), or from an unrelated donor. Donors are matched through special blood tests called HLA tissue typing.

Bone marrow is taken from the donor in the operating room while one is unconscious and pain-free (under general anaesthesia). Some of the donor’s bone marrow is removed from the top of the hip bone. The bone marrow is filtered, treated, and transplanted immediately or frozen and stored for later use. Then, transplant material is transfused into the patient through a vein and is naturally transported back into the bone cavities where it grows to replace the old bone marrow.

Alternatively, blood cell precursors, called stem cells, can be induced to move from the bone marrow to the blood stream using special medications. These stem cells can then be taken from the bloodstream through a procedure called leukapheresis.

The patient is prepared for transplantation by administering high doses of chemotherapy or radiation (conditioning). This serves two purposes. First, it destroys the patient’s abnormal blood cells or cancer. Second, it inhibits the patient’s immune response against the donor bone marrow (graft rejection).

Following conditioning, the patient is ready for bone marrow infusion. After infusion, it takes 10 to 20 days for the bone marrow to establish itself. During this time, the patient requires support with blood cell transfusions.

Wed,17 Dec 2003 05:30:00

Wed,17 Dec 2003 05:30:00

The major problem with bone marrow transplants (when the marrow comes from a donor, not the patient) is graft-versus-host disease. The transplanted healthy bone marrow cells may attack the patient’s cells as though they were foreign organisms. In this case, drugs to suppress the immune system must be taken, but this also decreases the body’s ability to fight infections.

Other significant problems with a bone marrow transplant are those of all major organ transplants – finding a donor and the cost. The donor is usually a sibling with compatible tissue. The more siblings the patient has, the more chances there are of finding a compatible donor.

Wed,17 Dec 2003 05:30:00

The patient will require attentive follow-up care for 2 to 3 months after discharge from the hospital. It may take 6 months to a year for the immune system to fully recover from this procedure.

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Bone marrow transplant – Doctor NDTV

Chemo-Boosting Drug Discovered for Leukemia – Futurism – Futurism

In BriefResearchers have discovered that acute myeloid leukemia causes leaking from the bone marrow that interferes with chemotherapy delivery. If chemotherapy for AML can be used together with drugs to treat this problem, outcomes may improve dramatically.

Researchers have discovered that the most common form of acute leukemia which strikes adults, acute myeloid leukemia (AML), prevents chemotherapy from being delivered properly by causing bone marrow to leak blood. This means that, by using drugs developed to treat blood vessel and heart problems in concert with chemotherapy, AML might be much more treatable. In this study, these drugs reversed bone marrow leaks in tissue from mice and humans, and also boosted chemotherapy effects. Since these drugs are already in clinical trials for other applications, the team hopes that they may be approved for use in the treatment of AML patients soon.

We found that the cancer was damaging the walls of blood vessels responsible for delivering oxygen, nutrients, and chemotherapy. When we used drugs to stop the leaks in mice, we were able to kill the cancer using conventional chemotherapy, Diana Passaro, Francis Crick Institute researcher and first author of the paper,said in a press release.

The team studied the ways in which AML affects bone marrow by injecting healthy mice with bone marrow from AML patients to create AML mice. They then used intravital microscopy to compare the bone marrow of AML mice with healthy mice and observed pre-loaded fluorescent dyes leaking from the bone marrow blood vessels into the AML mice. Next, they discovered that the cells lining the blood vessels in AML mice were oxygen-starved, which led to increases in nitric oxide (NO), a muscle relaxant. They realized this was probably causing the leaking, and provided NO blockers to the AML mice which slowed leukemia progress and extended remission.

The team not only helped chemotherapy drugs to reach their targets more effectively, but they also found that NO blockers increased stem cells in the bone marrow. This might help healthy cells out-compete cancerous cells, and improve treatment outcomes. Finally, the researchers found that an inability to reduce NO levels and chemotherapy failure were related.

With an average lifetime risk of less than half of one percent among the general population, AML is relatively rare. This is in addition to the fact that AML is a disease that primarily affects older people; the average age of AML patients in the US is 67, and the disease is even rarer before the age of 45. Despite this rarity, however, TheAmerican Cancer Society estimates that there will be around 21,380 new cases of AML in the US in 2017, and about 10,590 deaths, almost all in adults.

This high death rate is linked to the character of this form of cancer, which is particularly aggressive. This is in large part due to chemotherapy resistance and relapse, fewer than 25 percent of patients survive longer than five years after diagnosis. However, if this research leads to a new regimen of combined drug therapy, these numbers may change.

The team is optimistic about their findings and hopes to start clinical trials soon. Weve uncovered a biological marker for this type of leukemia as well as a possible drug target, Francis Crick Institute Group Leader and paper senior author Dominique Bonnet said in the press release. The next step will be clinical trials to see if NO blockers can help AML patients as much as our pre-clinical experiments suggest.

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Chemo-Boosting Drug Discovered for Leukemia – Futurism – Futurism

FDA Cracks Down on Stem Cell Clinics But Patients Are Still at Risk – TIME

On Monday, the U.S. Food and Drug Administration (FDA) announced that the agency is targeting clinics that offer unproven stem cell therapies, calling such offices “unscrupulous clinics” selling “so-called cures.” The FDA seized materials from one clinic in California, and sent a warning letter to another in Florida.

The FDA will not allow deceitful actors to take advantage of vulnerable patients by purporting to have treatments or cures for serious diseases without any proof that they actually work,” said FDA Commissioner Dr. Scott Gottlieb in a statement.

The agency announced that on Friday, Aug. 25th, U.S. Marshals seized five vials of a vaccine that is intended for people at a high risk for smallpox (for example, people in the military) from StemImmune Inc. in San Diego, California. The FDA says it learned that StemImmune was using the vaccines as well as stem cells from body fat to create an unapproved stem cell therapy. On its website, StemImmune says “The patients own (autologous, adult) stem cells, armed with potent anti-cancer payloads, function like a Trojan Horse, homing to tumors and cancer cells, undetected by the immune system.” The stem cell treatment was injected into the tumors of cancer patients at the California Stem Cell Treatment Centers in Rancho Mirage and Beverly Hills, California.

MORE: Three People Are Nearly Blind After Getting a Stem Cell Treatment

The FDA also sent a warning later to U.S. Stem Cell Clinic in Sunrise, Florida. The company recently came under public scrutiny when a March report revealed that three people had severe damage to their vision one woman went blindafter they were given shots of what the company said were stem cells into their eyes during a study sponsored by the clinic. The FDA says that an inspection of U.S. Stem Cell Clinic revealed that the clinic was using stem cells to treat diseases like Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), heart disease and pulmonary fibrosis. According to the FDA, there are currently only a limited number of stem cell therapies approved by the agencyincluding ones involving bone marrow, for bone marrow transplants in cancer care, and cord blood for specific blood-related disorders. There are no approved stem cell treatments for other diseases.

The FDA says U.S. Stem Cell Clinic also attempted to interfere with the FDA’s most recent inspection by refusing to allow FDA investigators to enter without an appointment, and denied the agency access to its employees. “Refusing to permit entry or FDA inspection is a violation of federal law,” the FDA says.

Action by the FDA on clinics promoting unproven stem cell therapies is “a long time coming,” says Sean Morrison, former president of the International Society for Stem Cell Research (ISSCR) and d irector of the Childrens Research Institute at UT Southwestern. “C linics are preying on the hopes of desperate patients claiming they can cure all manner of diseases with stem cells that have not been tested in clinical trials, and in some cases, are flat out impossible.”

In the past, medical experts were concerned over Americans traveling to countries with less medical regulation for stem cell therapies, but Morrison says such clinics have been popping up stateside over the last five years. “It’s not a few companies in the U.S. making claims about therapies with stem cells,” says Morrison. “It’s scores of companies. The problem has exploded in the U.S.”

Morrison blames the lack of FDA crackdown in the past for the growing problem. “At some point people made the calculation that the FDA didnt seem to be enforcing these laws,” he says. “The margins are huge. They charge people tens of thousands of dollars.”

Since stem cell therapy is still an active and legitimate area of scientific research, it can be hard for Americans to figure out what is safe and effective and what is not. Even when it comes to clinical trials, the scientific soundness is murky. A July 2017 paper reported that 18 U.S. companies have registered “patient-sponsored” stem cell studies on ClinicalTrials.gov. That means that the patients receiving the treatment paid for them, which isn’t the case in more legitimate studies. None of these were gold standard studies: meaning the people were not randomly assigned to receive the treatment or not, so the participants knew they were receiving the therapy that could bias the results. Only seven of the studies disclosed upfront that patients had to pay to join the study, and none revealed that the costs ranged from $5,000 to $15,000 a treatment, Wired reports.

While Morrison says he’s glad the FDA has taken action, he says it’s not enoughat least not yet. “The FDA has to show that there is really a sustained commitment to enforcement,” he says. “When the FDA wasnt bringing actions against these companies, I think people thought this meant that it was a gray area and that they could get away with it.”

Undoing that damage could be a long process, and one that Morrison says needs consistent attention by the agency. In a letter released on Monday, FDA commissioner Gottlieb said the agency is stepping up enforcement of stem cell therapies and regenerative medicine. “Ive directed the FDA to launch a new working group to pursue unscrupulous clinics through whatever legally enforceable means are necessary to protect the public health,” said Gottlieb. Whether those efforts have an impact remains to be seen.

Originally posted here:
FDA Cracks Down on Stem Cell Clinics But Patients Are Still at Risk – TIME

For Lowell native, stem cell match becomes a match as friends – Lowell Sun

From left to right: Richard Stone, a doctor at Dana-Farber Cancer Institute in Boston, poses with Peter Karalekas (center), 76, and Matthew Churitch, 22. Churitch donated stem cells to Karalekas two years ago, and he visited Dana-Farber with Karalekas earlier this summer. (Courtesy photo)

BOSTON — After winding his way through Massachusetts, Connecticut, New Hampshire and Maine for 76 years, Peter Karalekas has a proclamation: He’s a Southerner now.

He still lives in Kittery, Maine, just about an hour from the Lowell middle school where he taught for 21 years.

He has no plans to move.

Rather, Karalekas considers himself a Southerner because of his stem cells.

He never exactly felt all that sick.

Karalekas worked tirelessly for decades, first as a teacher and coach at the James S. Daley Middle School in Lowell and then as the owner of a half-dozen T-Bones restaurants across New Hampshire.

Even despite the 12-hour days, seven days a week, in the grind of the restaurant industry, Karalekas felt healthy and rarely fell ill.

Peter Karalekas, left, a 76-year-old former Lowellian, smiles during his first meeting with Matthew Churitch, 22, of Nashville, Tennessee, who helped save Karalekas life by donating stem cells. (Courtesy photo)

The two, who do not have children, moved to Kittery 17 years ago.

Everything started to change in 2014.

Karalekas recalls being “short-winded,” but he had very few other symptoms when he was diagnosed with myelodysplastic syndrome, a rare type of cancer in which the bone marrow is damaged and cannot produce enough blood cells.

The prognosis was not good.

“They said the only thing that would save me was a stem cell transplant,” Karalekas said. “Otherwise, I had a couple of months to live, because my cells were all dropping drastically.

He went onto a registry, hoping for a donor to pop up, but doctors told him it could take from six months to two years to find the right match. Even with a transplant, Karalekas said, his chances of success were “30 to 40 percent.”

The call came four weeks later.

Matthew Churitch got his call quickly, too.

He joined the National Marrow Donor Program’s Be the Match Registry in 2014, the summer between his freshman and sophomore years at Clemson University. His mother had been on the registry to donate for years. Churitch’s decision was simple: When a friend was diagnosed with leukemia, he knew he should sign up, too.

He did the requisite cheek swab, unsure if he would ever even be contacted to donate. By the time he had finished the following semester, he got the call.

A match was found.

Churitch went through several more levels of testing and preparation to donate stem cells to a stranger. He went to Clemson’s student health center to have blood drawn.

He returned to his native Nashville, Tennessee, going to a medical center 10 days in a row to receive shots in his stomach that would stimulate his bone marrow and prepare his cells for transplant.

He sat for eight hours, a needle in each arm as his stem cells were filtered out so they could be transferred to Boston.

“Getting the shots isn’t fun,” he said. “You’re pretty sore afterward for a few weeks. But knowing that the person on the other end is in hundreds and hundreds times more pain than any donor would ever go through — that kind of pushed me through.”

Karalekas and Churitch first connected via an anonymous letter, per the transplant registry’s rules, updating Churitch on Karalekas’s lengthy, isolated recovery. They were able to speak directly after a year.

Churitch dialed Karalekas’ number on a lengthy walk to class, took a deep breath and hit the call button. Moments later, both men were crying and laughing.

“That was really awesome, just being able to hear his voice and recognize that there’s somebody else on the other end of this,” Churitch said. “A lot of people don’t get the chance to connect with their recipients or their donors.”

Karalekas wanted more. He told his wife early on that he wanted to meet his “angel from heaven,” so when Churitch graduated Clemson earlier this year, Karalekas paid to bring the 22-year-old and his mother to New England.

In late June, Karalekas and his wife pulled into a pickup lane at Logan International Airport in Boston.

“I got out of the car, I charged over, and I gave them both a huge hug,” Karalekas said.

Karalekas showed Churitch and his mother around for five days.They went on a private tour of Fenway Park; they wandered the historic streets of Portsmouth, New Hampshire; they visited Dana-Farber together to meet the team that treated Karalekas.

Both families quickly bonded. Karalekas recalls his brother George asking Churitch about his portable phone charger, expressing curiosity about how convenient it was. A few weeks later, a brand-new portable charger arrived at George’s door, a gift from Churitch.

In January, Karalekas and his wife will vacation in Arizona and will cheer on Churitch’s mother — without Churitch even present — in the Phoenix Marathon.

Donor and recipient talk every week.

“It’s like we’re a very, very close-knit family now,” Karalekas said. “He’s the son we never had.”

Churitch is now in his first year at the University of South Carolina School of Medicine Greenville with hopes of becoming a physician. He hopes to use Karalekas’s experience as inspiration for any patients facing future hardship, and he hopes that others, especially young people, will see their success and join the registry.

“You never know where that will take you,” he said. “You can gain a friend for life, impact somebody and their family in need.”

Karalekas said he feels he has a new life: His chances of beating the disease are now 97 percent, he says, up from the 30 percent or 40 percent when he started treatment. Thanks to the transplant from a handsome, athletic college student in Tennessee.

“I said, ‘I’m a Southerner now,'” Karalekas said. “My stem cells are 99 percent this gentleman. I’m 99 percent him.”

Follow Chris on Twitter @ChrisLisinski.

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For Lowell native, stem cell match becomes a match as friends – Lowell Sun

Targeting bone marrow protein could be effective way to improve … – Gears Of Biz

Bone marrow contains hematopoetic stem cells, the precursors to every blood cell type. These cells spring into action following bone marrow transplants, bone marrow injury and during systemic infection, creating new blood cells, including immune cells, in a process known as hematopoiesis.

A new study led by University of Pennsylvania and Technical University of Dresden scientists has identified an important regulator of this process, a protein called Del-1. Targeting it, the researchers noted, could be an effective way to improve stem cell transplants for both donors and recipients. There may also be ways to modulate levels of Del-1 in patients with certain blood cancers to enhance immune cell production. The findings are reported this week in The Journal of Clinical Investigation.

Because the hematopoetic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and is easily manipulated, one can see that it could be a target in many potential applications, said George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Microbiology in Penns School of Dental Medicine and a senior author on the work.

I think that Del-1 represents a major regulator of the hematopoetic stem cell niche, said Triantafyllos Chavakis, co-senior author on the study and a professor at the Technical University of Dresden. It will be worthwhile to study its expression in the context of hematopoetic malignancy.

For Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine. Working with Chavakis, he had identified Del-1 as a potential drug target for gum disease after finding that it prevents inflammatory cells from moving into the gums.

Both scientists and their labs had discovered that Del-1 was also expressed in the bone marrow and began following up to see what its function was there.

In the beginning, I thought it would have a simple function, like regulating the exit of mature leukocytes [white blood cells]from the marrow into the periphery, Hajishengallis said, something analogous to what it was doing in the gingiva. But it turned out it had a much more important and global role than what I had imagined.

The researchers investigations revealed that Del-1 was expressed by at least three cell types in the bone marrow that support hematopoetic stem cells: endothelial cells, CAR cells and osteoblasts. Using mice deficient in Del-1, they found that the protein promotes proliferation and differentiation of hematopoetic stem cells, sending more of these progenitor cells down a path toward becoming myeloid cells, such as macrophages and neutrophils, rather than lymphocytes, such as T cells and B cells.

In bone marrow transplant experiments, the team discovered that the presence of Del-1 in recipient bone marrow is required for the transplanted stem cells to engraft in the recipient and to facilitate the process of myelopoesis, the production of myeloid cells.

When the researchers mimicked a systemic infection in mice, animals deficient in Del-1 were slower to begin making myeloid cells again compared to those with normal Del-1 levels.

We saw roles for Del-1 in both steady state and emergency conditions, Hajishengallis said.

Hajishengallis, Chavakis and their colleagues identified the protein on hematopoetic stem cells with which Del-1 interacts, the 3 integrin, perhaps pointing to a target for therapeutic interventions down the line.

The scientists see potential applications in bone marrow and stem cell transplants, for both donors and recipients. In donors, blocking the interaction between Del-1 and hematopoetic stem cells could enhance the mobilization of those progenitors into the bloodstream. This could be helpful for increasing donor cell numbers for transplantation. Transplant recipients, on the other hand, may need enhanced Del-1 interaction to ensure the transplanted cells engraft and begin making new blood cells more rapidly.

In addition, people undergoing chemotherapy who develop febrile neutropenia, associated with low levels of white blood cells, might benefit from the role of Del-1 in supporting the production of immune-related blood cells such as neutrophils.

Its easy to think of practical applications for these findings, said Hajishengallis. Now we need to find out whether it works in practice, so our studies continue.

Excerpt from:
Targeting bone marrow protein could be effective way to improve … – Gears Of Biz

Bacterial Infection Stresses Blood Stem Cells | Asian Scientist … – Asian Scientist Magazine

AsianScientist (Aug. 30, 2017) – In a study published in Cell Stem Cell, scientists in Japan and Switzerland have found that bacterial infections can stress blood-producing stem cells in the bone marrow and reduce their ability to self-replicate.

When a person becomes infected with a virus or bacteria, immune cells in the blood or lymph react to the infection. Some of these immune cells use sensors on their surfaces, called Toll-like receptors (TLR), to distinguish invading pathogens from molecules that are expressed by the host. By doing so, they can attack and ultimately destroy pathogens thereby protecting the body without attacking host cells.

Bone marrow contains hematopoietic stem cells which create blood cells, such as lymphocytes and erythrocytes, throughout the lifetime of an individual. When infection occurs, a large number of immune cells are activated and consumed. Hence, it is necessary to replenish these immune cells by increasing blood production in bone marrow.

Recent studies have revealed that immune cells are not the only cells that detect the danger signals associated with infection. Hematopoietic stem cells also identify these signals and use them to adjust blood production. However, little was known about how hematopoietic stem cells respond to bacterial infection or how it affected their function.

In this study, researchers from Kumamoto University and the University of Zurich analyzed the role of TLRs in hematopoietic stem cells upon bacterial infection, given that both immune cells and hematopoietic stem cells have TLRs.

To generate a model of bacterial infection, researchers injected one of the key molecules found in the outer membrane of gram negative bacteria and known to cause sepsislipopolysaccharide (LPS)into lab mice. They then analyzed the detailed role of TLRs in hematopoietic stem cell regulation by combining genetically modified animals that do not have TLR and related molecules, or agents that inhibit these molecules.

The results showed that LPS spread throughout the body, with some eventually reaching the bone marrow. This stimulated the TLRs of the hematopoietic stem cells and induced them to proliferate. They also discovered that while LPS promoted stem cell proliferation, it also induced stressed the stem cells, impairing their ability to successfully self-replicate and resulting in diminished blood production. Similar results were obtained after infection with Escherichia coli bacteria.

Fortunately we were able to confirm that this molecular reaction can be inhibited by drugs, said Professor Hitoshi Takizawa of Kumamoto University who led the study. The medication maintains the production of blood and immune cells without weakening the immune reaction against pathogenic bacteria. It might be possible to simultaneously prevent blood diseases and many bacterial infections in the future.

The article can be found at: Takizawa et al. (2017) Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness.

Source: Kumamoto University.Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Continued here:
Bacterial Infection Stresses Blood Stem Cells | Asian Scientist … – Asian Scientist Magazine

How your own stem cells could relieve your chronic pain – Good4Utah

Dr. Khan from Wasatch Pain Solutions gave us insight to Regenexx, the world’s most advanced stem cell and blood platelet procedures.

On what makesRegenexx treatments better than any other, Dr. Khan explained that a network of doctors and researchers have performed more stem cell related procedures than any other group in the United States; over 51,000 procedures. Which he says has lead them to producing over 50% of all available orthopedic stem cell research in the world.

Dr. Khan explained they only use a persons own living stem cells from their bone marrow along with their own blood platelets during their patented 3-step process. Studies show that bone marrow stem cells are vastly superior for orthopedic applications like helping to regenerate cartilage and heal tissue damage. The outcome that their process produces can help patients avoid surgery and maintain a very active lifestyle without severe pain.

For more information visit wasatchpainsolutions.com or call (801) 302-2690.

This story includes sponsored content.

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How your own stem cells could relieve your chronic pain – Good4Utah

Why Doug Baldwin went to England for stem-cell therapy – The News Tribune (blog)

RENTON Turns out, Doug Baldwin started this current Seahawks fad of traveling outside the teams normal medical coverage to get far-flung treatment using body cells.

The Seahawks No. 1 wide receiver told me Monday he went overseas before this season — to England, to be exact — for pre-emptive, preventative treatment to maintain healthy knees.

I had mine in the offseason. I did stem-cell, Baldwin said, drenched in sweat in the hallway outside the teams locker room just after completing Mondays practice.

I mean, I dont have any ailments. Im trying to find every edge I can get.

Baldwin, Seattles $46 million receiver, tied Bobby Engrams 2007 franchise record with 94 receptions last season. He earned his first Pro Bowl selection. In 2015, the season that led to his contract extension, he co-led the NFL with 14 touchdown catches.

He said hed been looking into stem-cell therapy for years.

Transplanting or using bone marrow is the most widely used stem-cell therapy to treat or prevent a condition or disease. The U.S. Food and Drug Administration further explains stem cells may also help repair the body by dividing to replenish cells that are damaged by disease, injury, or normal wear.

So why London for Baldwin?

The FDA, as stated on its website, has not approved any stem cell-based products for use in this country other than using human umbilical cord blood forming stem cells for certain diseases.

There was a company wed be speaking to, Baldwin said of the London place he got treatment, without wanting to disclose many details. Did my research. Took my two years to finally decide.

In the last two weeks, seven Seahawks have gone away and outside the teams regular medical treatment to get a debated blood-re-injection process called regenokine to treat aching joints and/or aid in recovery from surgery. The treatment was founded in Germany, where its known as orthokine.

K.J. Wright returned last week from regenokine treatment, the re-injection of ones blood after it is heated and spun in a centrifuge to enhance its anti-inflammatory properties. The Pro Bowl outside linebacker played in Seattles exhibition last Friday against Kansas City.

D.J. Alexander the Pro Bowl special-teams player the Seahawks acquired this summer in a trade with Kansas City, went for regenokine treatment last week.

On Monday, coach Pete Carroll said wide receiver and kick returner Tyler Lockett, Pro Bowl defensive ends Michael Bennett and Cliff Avril, starting left guard Luke Joeckel and starting outside linebacker Michael Wilhoite are away from the team getting the same treatment Wright and Alexander had. Carroll said the team expects all those players to be ready for the opening game Sept. 10 at Green Bay.

That process reportedly costs $10,000. That doesnt count the travel and hotel costs of flying to get the therapy, of course. The FDA has yet to approve regenokine for use in the U.S., largely because its still unproven and reportedly because the agency has issues with the heating of the blood.

That is probably why Carroll said this on Thursday: Ive never had the OK that I can talk about it; I dont even know if I can talk about it. I was always afraid I wouldnt pronounce it right. But what I know its called is regenokine.

Dr. Peter Wehling in Germany, the man who founded the procedure known there as orthokine, was said in 2013 to have treated 30 to 40 NFL players with it. At that time the treatment process took four days, which could explain why Wright and his Seahawks successor have been missing a week of practices and games this month for it.

LifeSpan Medicine, clinic in Santa Monica, California, with offices also in New York and Dallas, lists regenokine as one the regenerative therapies it practices — again, without FDA approval for use in this country.

Carroll said this on Monday:

Baldwin turns 29 next month. The opening at the Packers will begin the second season of the four-year, $46 million extension he signed in the summer of 2016. He looked ready for the 2017 season in Seattles most recent preseason game, Friday against Kansas City. He had two catches for 45 yards in 2 1/2 quarters, racing across the field and away from Chiefs defenders.

Hes only missed two games in his six-year career. Those absences were in his second season, 2012, after Seattle signed him as one of the leagues most successful undrafted free agents of the last decade.

Now, hes one of the trend-setters among eight Seahawks whove received alternative therapy.

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Why Doug Baldwin went to England for stem-cell therapy – The News Tribune (blog)

FDA moves to curb dangerous stem cell clinics – Philly.com

The U.S. Food and Drug Administration on Monday announced a crackdown on deceptive and dangerous stem cell clinics, starting with actions against a California company accused of giving smallpox vaccine to cancer patients, and a Florida company that ruined the eyesight of three women.

Our actions today should also be a warning to others who may be doing similar harm, FDA Commissioner Scott Gottlieb said in a statement, urging consumers and health-care providers to report rogue clinics and injuries.

FDA Commissioner Scott Gottlieb

The California company, San Diego-based StemImmune Inc., was combining the vaccine with stem cells derived from fat, then giving it intravenously or injecting it into tumors of cancer patients at clinics in Rancho Mirage and Beverly Hills, Calif., the FDA said.

U.S. marshals on Friday seized five vials of smallpox vaccine, including one that was partially used. The agency is investigating how the company obtained the vaccine, which has been stockpiled by the government in case of a bioterrorist attack.

The vaccine is made with live vaccinia virus, a poxvirus similar to but less harmful than smallpox. The vaccine could cause life-threatening problems in immune-compromised cancer patients, and alsoin certain unvaccinated people who might be accidentally infected by the patients, the FDA explained.

Speaking as a cancer survivor, Gottlieb said in a statement, I know all too well the fear and anxiety the diagnosis of cancer can have and how tempting it can be to believe the hollow claims made by these kinds of unscrupulous clinics. The FDA will not allow deceitful actors to take advantage of vulnerable patients.

In a separate enforcement action, the FDA sent a warning letter last week to U.S. Stem Cell Clinic of Sunrise, Fla., saying it could face product seizure or an injunction. Agency inspectors found that the clinic was processing fat-derived stem cells and claiming to treat a raft of conditions, including Parkinsons disease, amyotrophic lateral sclerosis (ALS), rheumatoid arthritis, diabetes, and heart failure.

In March, U.S. Stem Cell made headlines when an article in the New England Journal of Medicine reported that three women with age-related macular degeneration suffered severe and permanent vision damage one was blinded after stem cells were injected into their eyeballs at the clinic. The article was written by doctors unconnected with the clinic who treated the women for the disastrous results.

Critics of unapproved stem cell treatments have called for tougher oversight by the FDA, as well as by the Federal Trade Commission, which regulates advertising, and by state medical boards, which oversee the practice of medicine.

The regulatory moves come as so-called regenerative medicine is exploding, spawning an industry built on unproven treatments using stem cells from bone marrow or fat. In recent months, networks of chiropractors have run big-budget ads for such treatments in newspaper across the country, including the Inquirer. Those ads, however, focus on addressing orthopedic problems such as degenerative discs and arthriticknees.

The only FDA-approved stem cell therapies involve using cells from bone marrow or umbilical cord blood to treat blood cancers and certain immune disorders. In general, biologic tissues that are processed and marketed as therapies are supposed to go through the FDAs drug approval process, which involves years of costly clinical testing in humans.

However, the FDA has tried to find a middle ground, recognizing the potential promise of stem cells in tissue repair and regeneration. The FDA has published, but has not finalized, draft guidance for stem cell products, saying they can be exempted from the drug approval process under certain scenarios. Among other criteria, the cells must be minimally manipulated and used in a homologous way, meaning for the same function they perform naturally in the body.

In a policy statement issued Monday, Gottlieb promised that this fall, the agency will advance a comprehensive policy framework that will more clearly describe the rules of the road for this new field. It will enable responsible product developers to gain FDAapproval with minimal burdens and costs.

We want to facilitate innovation, he wrote.

Published: August 28, 2017 4:42 PM EDT

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FDA moves to curb dangerous stem cell clinics – Philly.com

MS sufferer gets pioneering stem cell treatment – Gloucestershire Live

Multiple sclerosis sufferer Roy Palmer is about to embark on the next phase of his pioneering treatment.

But it comes with risks he is prepared to take in the hope it will cure the debilitating condition.

The 43-year-old father of two from Quedgeley is determined it will work. He was diagnosed with relapsing remitting MS but now has the secondary progressive form of the disease, which means it gets steadily worse.

He said: I fought for a year to get hematopoietic stem cell transplantation and many people told me I didnt fit the criteria but I didnt let that stop me.

Mr Palmer had a week of injections to draw the stem cells from his bone marrow.

He and his wife Helen travelled to Hammersmith Hospital in London where he was given a day of chemotherapy.

Mr Palmer lost his hair as a result and was left feeling sick and tired.

The stem cells have been frozen and will be reintroduced to his body after another aggressive course of chemotherapy.

It will be fed directly into a main artery in his chest before Mr Palmer spends the next four weeks in isolation.

He will start the treatment on September 18 his 24th wedding anniversary.

Mr Palmer said: Im not someone to sit around and feel sorry for myself.

If the treatment works then, oh my God, I couldnt begin to describe what it would mean to me.

He added: To be able to walk out of my front door would mean the world.

I know Im lucky to be able to get the treatment. Im worried, my immune system will be obliterated, but I have to give this everything. Im a fighter and determined to make this work.

Mr Palmers family back his decision to undergo HSCT treatment, although they worry about the effect it will have.

His 45-year-old wife said: When they give the chemotherapy it brings the body back down to zero.

It will stop any immune system and take some time for the body to start getting back to normal.

When Roys levels are up they will start to reintroduce the stem cells.

The MS Society website says HSCT aims to reset the immune system to stop it attacking the central nervous system.

It uses chemotherapy to remove the harmful immune cells and then rebuilds the immune system using haematopoietic stem cells found in bone marrow.

They can produce all the different cells in the blood.

Mrs Palmer said: Im happy for Roy to take that risk and to support him but it is a lethal dose of chemo.

The treatment can be done abroad and costs around 60,000. In the past we were considering that option but there is no aftercare.

The couples daughter Abi, 12, said: I feel a little scared for dad but okay. I cant remember him walking.

And 20-year-old son Jack said: Dad has been in a chair for about 10 years and to see him walk again would mean everything.

Just standing next to each other would mean the world.

Once the stem cells are back in Mr Palmers body the hope is he will make a full recovery and be free of MS,

He said: It will be great to not have to ask people to do things for me.

I do what I can but I dont like to hang around waiting.

I want people to know there is treatment and it can be a fight but Ive got to do this now.

Continue reading here:
MS sufferer gets pioneering stem cell treatment – Gloucestershire Live

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