Everyone loves a medical mystery, except the afflicted patient and his or her family who shuffle from doctor to doctor in search of an explanation for a disorder whose name, origin, prognosis and cure are all unknown. Now, the National Institutes of Health have underwritten a nationwide "whodunnit" campaign, with a $43 million-initiative to fund the diagnosis and exploration of undiagnosed, unrecognized and misunderstood diseases.

Think of it as a bid to clear a backlog of medical cold cases, using dazzling new tools now at the disposal of medical sleuths. Think of it also as an opportunity for scientists to glean new insights into the human genome and its role in causing -- and perhaps curing -- disease.

This week, the NIH announced the expansion of its Undiagnosed Disease Network, which by the summer of 2017 is expected to enroll at least 300 new patients with mysterious and intractable conditions per year, nationwide.

The diseases that afflict these patients are conditions that have stumped even skilled physicians. Doctors may fail to recognize the conditions because they are rarely seen, have never been described in the medical literature or are rare forms of more common diseases. Some may be caused outright by infection or environmental exposure. But many will have their origins in a patient's genes but have been unexpressed or gone undetected earlier in the patient's family tree.

Prospective patients interested in participating in the Undiagnosed Diseases Network may learn more here.

The initiative builds on a pilot program run for six years from NIH's Bethesda, Md., clinical center. There, some 600 patients whose symptoms have stumped their doctors have been brought in for extensive diagnostic work-ups in a bid to identify and treat their diseases.

Using genomic analysis and a full toolbox of standard diagnostic tests, the multidisciplinary clinical and research team has diagnosed approximately 100 patients. In the process, the NIH team discovered two unknown diseases and identified 15 genes not previously associated with any other human disease.

Now, the experts at NIH will be joined in the hunt by physician/scientists at six institutions across the country -- Baylor College of Medicine in Houston; Boston Children's Hospital, Brigham and Women's Hospital, and Massachusetts General Hospital in Boston; Duke University in Durham, N.C.; Stanford University; UCLA; and Vanderbilt University Medical Center in Nashville, Tenn.

The expansion of the mystery diseases network comes at a time that scientists could only dream about when the Human Genome Project was launched in 1990. Today, genomic analysis -- faster, cheaper, more comprehensive and more reliable than ever before -- is finding its way into clinical practices.

The genetic analysis of solid tumors is widely used to guide the choice of targeted treatments for cancer. The microbiota of everything from human guts to combat wounds is being genetically characterized by the new techniques. Scientists are using them to uncover the fingerprints of ancient plagues and plot the course of prehistoric human migration. And a new generation of massively parallel computer technology has made it possible to sequence a human being's 3 billion base pairs of DNA in a day -- at a cost of less than $5,000.

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Medical sleuths seek patients with mystery diseases, offer new tools

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Lets Play The Sims 3 Perfect Genetics Part 6: Baby #1
Watch as the first child is born. Will it be the Perfect Genetic Heir? My Sims 3 Page: http://mypage.thesims3.com/mypage/becky050890 My Husband #39;s Sims 3 Page...

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The Sims 3 | Perfect Genetics Challenge Part 10: Heir?
In this part, you #39;ll have to find out for yourself 😉 dont hurt me ily Backstory: "Once upon a time, the Mighty Player sent a Sim to live in the world where all its creations were living...

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Amy on faith, genetics, and opportunities for discussion
Amy talks about the sometimes complicated intersection between genetics and faith and the value of discussion about genetics and the sticky ethical questions...

By: Personal Genetics Education Project - pgEd.org

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The Most Tough German Shepherd Puppy/ Puppy Test/ Top Genetics/ Top Breeding
In this video you see one of my puppies that is 6 weeks old getting tested for the first time. What I am looking for when I am testing a puppy is the top genetic traits. Let me explain to you..I...

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The Most Tough German Shepherd Puppy/ Puppy Test/ Top Genetics/ Top Breeding - Video

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ACGT president and co-founder, Barbara Netter, at left, with Savio L.C. Woo, founding chair, ACGT Scientific Advisory Council and professor at the Mt. Sinai School of Medicine.

Barbara Netter and her late husband Edward Netter have been awarded the American Society of Gene and Cell Therapy (ASGCT) Distinguished Service Award for their contributions to the field of genetic and cellar therapy.

As the founders of Alliance for Cancer Gene Therapy (ACGT), the Netters have helped grant almost $25 million in funding to cancer researchers and physicians worldwide. The award was presented during the 17th annual meeting of the ASGCT May 22, in front of some 1,700 scientists and cancer research advocates.

Its an honor to receive this accolade from an organization at the center of our medical community, Ms. Netter said in a statement. Through the work at ACGT and in the cell and gene therapy realm, I have the rare opportunity to see new and optimistic methods of treating cancer unfold. With fantastic breakthroughs in cancer cell and gene therapy occurring more frequently, the future is bright.

Founded in 1998, the ASGCT is a non-profit medical organization dedicated to boosting awareness for gene and cell therapies. These therapies have been shown to be effective against cardiovascular, genetic, infectious and degenerative disorders in addition to cancer. ASGCT publishes the medical journal Molecular Therapy to report on the latest advancements in the field.

The ASGCT Advisory Council selected Barbara and Edward Netter (posthumously) for this award based on the founding of ACGT and the enormous contributions made to advancing cancer gene therapy research, ASGCT advisory council chair Terence R. Flotte said.

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Philanthropists honored for service

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Medicine Based on Your Genetic Makeup
Personalized medicine is upending hierarchies with consumer products like Scanadu, designed to track physiological signals, and 23andMe.com, which provides raw genetic data. Meanwhile, our...

By: The Aspen Institute

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From Horizontal to Vertical Thinking: Interpreting a Diagnosis
Personalized medicine is upending hierarchies with consumer products like Scanadu, designed to track physiological signals, and 23andMe.com, which provides raw genetic data. Meanwhile, our...

By: The Aspen Institute

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How Same-Day Test Results Could Revolutionize the Health Industry
Personalized medicine is upending hierarchies with consumer products like Scanadu, designed to track physiological signals, and 23andMe.com, which provides raw genetic data. Meanwhile, our...

By: The Aspen Institute

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GoldLab Symposium 2010 - Daniel Kracov
Daniel Kracov, J.D., Partner, Arnold and Porter spoke at GLS2010. His presentation: "Personalized Medicine: Facilitating a Partnership with the FDA"

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Bubba sings with Max Renshaw at Lew Reed Spinal Cord Injury Fund Benefit 6-28-14
Thanks to all of Bubba #39;s friends, Sunny Jo Loudin, Rich Edwards Puyallup Eagles volunteers who helped raise funds for victims of spinal cord injuries.

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The STAP stem cell saga has reached its bitter conclusion for now.

The authors of two papers published by the journal Nature, which claimed to have produced embryonic-like stem cells from adult cells, have retracted them.

The papers said that almost any adult cell could be coaxed into becoming a stem cell just by dipping them in a bath of acid for 30 minutes. The method held great promise for regenerative medicine because it could be used to create any cell without needing to reprogram genes, or destroy an embryo. The team, led by researchers at the Riken Institute in Kobe, Japan, called this technique stimulustriggered acquisition of pluripotency, or STAP.

But in the months after publication, no independent team was able to replicate the experiments. Instead, the researchers around the world scrutinising the papers exposed many flaws in the papers including manipulated pictures of protein gel panels and mislabelled images. A public flogging of many high profile researchers ensued (see ""How the STAP cell story unfolded", below) and Nature's review process was thrust into the spotlight.

The journal published two statements today from the authors saying they were retracting both papers. The statements include an apology from the authors, in which they admit that multiple errors impair the credibility of the study. They concede that they are unable to say without doubt whether the STAP cell phenomenon is real.

An accompanying Nature editorial says that in practice, it may be impossible for journals to police gel panels routinely "without disproportionate editorial effort". The journal says it is now reviewing its screening practices to increase such checks.

The editorial goes on to say that Nature believes that its editors and referees could not have detected the fatal faults in this work. However, it emerged during the investigation that the papers were first submitted for publication in Science. According to a Nature News blog, Science rejected them after spotting the manipulated images and warning the lead author of the papers, Haruko Obokata, that such composite images need to be marked. Soon after the papers were published, independent bloggers started finding discrepancies in the work.

The Nature editorial states that the episode has highlighted flaws in Nature's procedures. The journal says that it needs to put quality assurance even higher on its agenda to make sure that people's trust in science is not betrayed.

Charles Vacanti at Harvard Medical School, one of the authors on the papers, has said that he is deeply saddened by the whole episode, although he continues to believe that none of the issues cast doubt on the existence of STAP cells themselves. He says he is encouraged that Riken president Ryoji Noyori and other independent labs will now allow sufficient time to try to replicate the experiments.

29 January Two high profile papers are published in Nature claiming that adult cells could be coaxed into becoming stem cells by dipping them in a bath of acid for 30 minutes. The team call these new cells stimulustriggered acquisition of stem cells, or STAP cells.

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Acid-bath stem cell papers are finally retracted

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Stem cell scientists had what first appeared to be an easy win for regenerative medicine when they discovered mesenchymal stem cells several decades ago. These cells, found in the bone marrow, can give rise to bone, fat, and muscle tissue, and have been used in hundreds of clinical trials for tissue repair. Unfortunately, the results of these trials have been underwhelming. One problem is that these stem cells don't stick around in the body long enough to benefit the patient.

But Harvard Stem Cell Institute (HSCI) scientists at Boston Children's Hospital aren't ready to give up. A research team led by Juan Melero-Martin, PhD, recently found that transplanting mesenchymal stem cells along with blood vessel-forming cells naturally found in circulation improves results. This co-transplantation keeps the mesenchymal stem cells alive longer in mice after engraftment, up to a few weeks compared to hours without co-transplantation. This improved survival gives the mesenchymal stem cells sufficient time to display their full regenerative potential, generating new bone or fat tissue in the recipient mouse body. The finding was published in the Proceedings of the National Academy of Sciences (PNAS).

"We are losing mesenchymal stem cells very rapidly when we transplant them into the body, in part, because we are not giving them what they need," said Melero-Martin, an HSCI affiliated faculty member and an assistant professor of surgery at Boston Children's Hospital, Harvard Medical School.

"In the body, these cells sit very close to the capillaries, constantly receiving signals from them, and even though this communication is broken when we isolate mesenchymal stem cells in a laboratory dish, they seem to be ok because we have learned how to feed them," he said. "But when you put the mesenchymal stem cells back into the body, there is a period of time when they will not have this proximity to capillary cells and they start to die; so including these blood vessel-forming cells from the very beginning of a transplantation made a major difference."

Melero-Martin's research has immediate translational implications, as current mesenchymal clinical trials don't follow a co-transplantation procedure. He is already collaborating with surgical colleagues at Boston Children's Hospital to see if his discovery can help improve fat and bone grafts. However, giving patients two different types of cells, as opposed to just one, would require more time and experiments to determine safety and efficacy. Melero-Martin is seeking to identify the specific signals mesenchymal stem cells receive from the blood vessel-forming cells in order to be able to mimic the signals without the cells themselves.

"Even though mesenchymal stem cells have been around for a while, I think there is still a lack of fundamental knowledge about communication between them and other cells in the body," he said. "My lab is interested in going even beyond what we found to try to understand whether these cell-cell signals are different in each tissue of the body, and to learn how to educate both blood vessel-forming and mesenchymal stem cells to co-ordinate tissue specific regenerative responses."

Other Harvard Stem Cell Institute researchers are studying mesenchymal stem cells as bioengineering tools to deliver therapeutics, which is possible because of the cell type's unique ability to not trigger an immune response. Jeffrey Karp, PhD, at Brigham and Women's Hospital has developed several methods to turn these cells into drug-delivery vehicles, so that after transplantation they can, for example, hone in on swollen tissue and secrete anti-inflammatory compounds. And Khalid Shah, PhD, at Massachusetts General Hospital has designed a gel that holds mesenchymal stem cells in place so that they can expose brain tumors to cancer-killing herpes viruses.

"A lot of these applications have no real direct link with mesenchymal stem cells' supposed progenitor cell function," Melero-Martin said. "In our study, we went back to the collective ambition to use these cells as a way to regenerate tissues and we are not in a position to say how that affects other uses that people are proposing."

Story Source:

The above story is based on materials provided by Harvard University. Note: Materials may be edited for content and length.

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Research team pursues techniques to improve elusive stem cell therapy

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1-Jul-2014

Contact: Krysten Carrera krysten.carrera@nih.gov 301-435-8112 The JAMA Network Journals

Use of a lower intensity bone marrow transplantation method showed promising results among 30 patients (16-65 years of age) with severe sickle cell disease, according to a study in the July 2 issue of JAMA.

Myeloablative (use of high-dose chemotherapy or radiation) allogeneic hematopoietic stem cell transplantation (HSCT; receipt of hematopoietic stem cells "bone marrow" from another individual) is curative for children with severe sickle cell disease, but associated toxicity has made the procedure prohibitive for adults. The development of nonmyeloablative conditioning regimens (use of lower doses of chemotherapy or radiation to prepare the bone marrow to receive new cells) may facilitate safer application of allogeneic HSCT to eligible adults, according to background information in the article.

Matthew M. Hsieh, M.D., of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md., and colleagues explored a nonmyeloablative approach in a pilot group of 10 adults with severe sickle cell disease, using a simplified HSCT regimen (with stem cell donation from a immunologically matched sibling), that had few toxic effects, yet all patients continued taking immunosuppression medication. The researchers have since revised the protocol to include an option to stop immunosuppression after 1 year in selected patients (those with donor CD3 engraftment of greater than 50 percent and normalization of hemoglobin). In this report, the authors describe the outcomes for 20 additional patients with severe sickle cell disease, along with updated results from the first 10 patients. All 30 patients (ages 16-65 years) were enrolled in the study from July 2004 to October 2013.

As of October 25, 2013, 29 patients were alive with a median follow-up of 3.4 years, and 26 patients (87 percent) had long-term stable donor engraftment without acute or chronic graft-vs-host disease. Hemoglobin levels improved after HSCT; at 1 year, 25 patients (83 percent) had full donor-type hemoglobin. Fifteen engrafted patients discontinued immunosuppression medication and had no graft-vs-host disease.

The average annual hospitalization rate was 3.2 the year before HSCT, 0.63 the first year after, 0.19 the second year after, and 0.11 the third year after transplant. Eleven patients were taking narcotics long-term at the time of transplant. During the week they were hospitalized and received their HSCT, the average narcotics use per week was 639 mg of intravenous morphine-equivalent dose. The dosage decreased to 140 mg 6 months after the transplant.

There were 38 serious adverse events including pain, infections, abdominal events, and toxic effects from the medication sirolimus.

"In this article, we extend our previous results and show that this HSCT procedure can be applied to older adults, even those with severe comorbid conditions " the authors write. "These data reinforce the low toxicity of this regimen, especially among patients with significant end-organ dysfunction."

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Bone marrow transplantation shows potential for treating adults with sickle cell disease

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UVA joins National Marrow Donor Program giving greater access to cancer treatments by Ishaan Sachdeva | Jun 25 2014 | 06/25/14 10:11pm | Updated 06/30/14 9:56pm

The Emily Couric Cancer Center of the University of Virginia Health System has expanded its access to bone marrow and hematopoietic stem cell transplant donors. Now designated as a National Marrow Donor Program (NMDP), the Health System will have access to the Be The Match Registry, the worlds largest and most diverse bone marrow registry. Implications of this change are significant for patients afflicted with blood cancers like leukemia who obtain treatment through the Health System.

Bone marrow, the soft, spongy tissue within bones like the sternum or the ilium of the pelvis, forms hematopoietic or blood-forming stem cells. These cells, unlike embryonic stem cells, differentiate only into types of blood cells- red blood cells, white blood cells or clotting platelets. Leukemia causes bone marrow to produce abnormal, leukemic white blood cells that divide uncontrollably, forming tumors that deprive cells of oxygen and reduce infection defense. One treatment method is autologous bone marrow transplant, in which patients receive stem cells from their healthy, non cancerous bone marrow.

The idea [of autologous transplants] is that you extract healthier bone marrow from the patient to have a source of stored, non-cancerous bone marrow. You can then treat the patient with higher doses of treatment than you can normally give because the most common limitation to treatment is that treatment will kill off healthy bone marrow you might have, said Thomas P. Loughran Jr., MD, the Universitys Cancer Center director.

Essentially, a patients healthy bone marrow is safeguarded outside their body while aggressive treatment is administered to kill cancerous marrow. Another form of treatment is allogeneic treatment, in which bone marrow is transplanted from a sibling or an unrelated donor.

In an allogeneic transplant, you are also transplanting in a new immune system. The new immune system comes in and recognizes the body as a foreign tissue and starts attacking that tissue. This causes a beneficial graft vs. leukemia effect where this new immune system attacks any residual leukemia, but may also cause a harmful graft versus host disease where normal tissue is also attacked, Loughran said.

The donor and recipient tissue interaction underscores the genetic component of bone marrow transplants from external donors. Despite the curative potential of a bone marrow transplant, a strong genetic match between donor and recipient is crucial to the utility of a transplant.

The ability of any donor to be successful is based on genetics. Its called HLA [human leukocyte antigen] typing. The HLA system has four genes called A, B, C and D, and it turns out that A, B and D are influential. We have half of our genes each from both parents, so we have six of these: 2 A, 2 B and 2 D. The best case is a six out of six match from a brother or sister, but the chances are only 1 in 4, said Loughran. The consequence of low genetic probabilities is a large pool of unrelated donors, like the Be The Match Registry. Through such services, patients have a greater chance of finding an unrelated donor who may provide a successful genetic match.

The coordinating center would identify the place where the donor is living and tell them they are potentially able to donate. In the past, the donor would have bone marrow directly extracted. Now it is almost always from the PBSCT [peripheral blood stem cell transplantation] procedure. The donor takes a growth factor that stimulates growth of the needed hematopoietic stem cells within their peripheral blood circulation. A catheter collects this blood and the stem cells are separated from the blood by a machine, and the blood is returned back to the donor. The collected stem cells are sent to the lab where they are purified and frozen, Loughran said.

Meanwhile, the patient in preparation for the transplant is given the highest dose of chemotherapy that can be tolerated. The donated stem cells are administered to the patient in a way similar to IV fluid.

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UVA Expands Cancer Treatment

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Bone marrow transplants can reverse severe sickle cell disease in adults, a small study by government scientists found, echoing results from a similar technique used in children.

The researchers and others say the findings show that age need not be a barrier and that the technique could change practice for some adult patients when standard treatment fails.

The transplant worked in 26 of 30 adults, and 15 of them were able to stop taking drugs that prevent rejection one year later.

"We're very pleased," said Dr. John Tisdale, the study's senior author and a senior investigator at the National Institutes of Health. "This is what we hoped for."

Sickle cell disease is a genetic condition that damages oxygen-carrying hemoglobin in red blood cells that then form sickle shapes that can block blood flow through veins. It can cause anemia, pain and organ damage. The disease affects about 100,000 Americans and millions worldwide.

The treatment is a modified version of bone marrow transplants that have worked in kids. Donors are a brother or sister whose stem cell-rich bone marrow is a good match for the patient.

Tisdale said doctors have avoided trying standard transplants in adults with severe sickle cell disease because the treatment is so toxic. Children can often tolerate it because the disease typically hasn't taken as big a toll on their bodies, he said.

The disease is debilitating and often life-shortening. Patients die on average in their 40s, Tisdale said. That's one reason why the researchers decided to try the transplants in adults, hoping the technique could extend their lives.

The treatment involves using chemotherapy and radiation to destroy bone marrow before replacing it with healthy donor marrow cells. In children, bone marrow is completely wiped out. In the adult study, the researchers only partially destroyed the bone marrow, requiring less donor marrow. That marrow's healthy blood cells outlast sickle cells and eventually replace them.

Results from the adult study, involving patients aged 29 on average, were published Tuesday in the Journal of the American Medical Association.

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Study finds new treatment for adult sickle cell disease

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The treatment could edge out joint replacement procedures to a large extent.

Hyderabad, June 30:

A team of doctors from a city hospital have harvested stem cells of a person using bone marrow from the pelvis area to replace some dead tissues in the hip. By doing this, they saved the patient from undergoing a hip replacement.

The Apollo Health City team, headed by orthopaedic specialist Paripati Sharat Kumar, diagnosed a 39-year-old women suffering from Avascular Necrosis. Her condition would require undergoing a replacement of hips.

After assessing her condition, the team has decided to go for the autologous stem cell procedure (where donor and the receiver is the same person) to save both the hip joints.

The minimally invasive procedure involved taking bone marrow aspirate from the patients pelvis. Stem cells were harvested from the aspirate through a process that takes about 15 minutes. Stems cells were planted in the area of damage under fluoroscopy control following core decompression, Kumar said in a statement on Monday.

He feels that the autologous stem cell treatment could edge out joint replacement procedures to a large extent in the days to come. The scope of this procedure in orthopaedics and sports medicine is enormous. This could be extended to indications including osteoarthritis of knee, shoulder, hip, elbows, ankle and spine, he said.

(This article was published on June 30, 2014)

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Autologous stem cell treatment could be the road ahead

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About seven days after conception, something remarkable occurs in the clump of cells that will eventually become a new human being. They start to specialize. They take on characteristics that begin to hint at their ultimate fate as part of the skin, brain, muscle or any of the roughly 200 cell types that exist in people, and they start to form distinct layers.

Although scientists have studied this process in animals, and have tried to coax human embryonic stem cells into taking shape by flooding them with chemical signals, until now the process has not been successfully replicated in the lab. But researchers led by Ali Brivanlou, Robert and Harriet Heilbrunn Professor and head of the Laboratory of Stem Cell Biology and Molecular Embryology at The Rockefeller University, have done it, and it turns out that the missing ingredient is geometrical, not chemical.

Understanding what happens in this moment, when individual members of this mass of embryonic stem cells begin to specialize for the very first time and organize themselves into layers, will be a key to harnessing the promise of regenerative medicine, Brivanlou says. It brings us closer to the possibility of replacement organs grown in petri dishes and wounds that can be swiftly healed.

In the uterus, human embryonic stem cells receive chemical cues from the surrounding tissue that signal them to begin forming layers a process called gastrulation. Cells in the center begin to form ectoderm, the brain and skin of the embryo, while those migrating to the outside become mesoderm and endoderm, destined to become muscle and blood and many of the major organs, respectively.

Brivanlou and his colleagues, including postdocs Aryeh Warmflash and Benoit Sorre as well as Eric Siggia, Viola Ward Brinning and Elbert Calhoun Brinning Professor and head of the Laboratory of Theoretical Condensed Matter Physics, confined human embryonic stem cells originally derived at Rockefeller to tiny circular patterns on glass plates that had been chemically treated to form micropatterns that prevent the colonies from expanding outside a specific radius. When the researchers introduced chemical signals spurring the cells to begin gastrulation, they found the colonies that were geometrically confined in this way proceeded to form endoderm, mesoderm and ectoderm and began to organize themselves just as they would have under natural conditions. Cells that were not confined did not.

By monitoring specific molecular pathways the human cells use to communicate with one another to form patterns during gastrulation something that was not previously possible because of the lack of a suitable laboratory model the researchers also learned how specific inhibitory signals generated in response to the initial chemical cues function to prevent the cells within a colony from all following the same developmental path.

The research was published June 29 in Nature Methods.

At the fundamental level, what we have developed is a new model to explore how human embryonic stem cells first differentiate into separate populations with a very reproducible spatial order just as in an embryo, says Warmflash. We can now follow individual cells in real time in order to find out what makes them specialize, and we can begin to ask questions about the underlying genetics of this process.

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Using Geometry, Researchers Coax Human Embryonic Stem Cells to Organize Themselves

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The Cell Therapy Catapult Official Opening Event
The Cell Therapy Catapult official opening event was a great succes with many colleagues from industry, government and universities attending including RT Hon Dr. Vince Cable MP, Secretary...

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The Cell Therapy Catapult Official Opening Event - Video

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How to Grow Your Hair Faster and Longer: Ovation Cell Therapy
Here is a review/how to on how i #39;ve been growing my hair with ovation cell hair therapy. I cut 6.5 inches in december which was A LOT! So now I #39;m on the trac...

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A new approach demonstrated that the recognition of unique cancer mutations appeared to be responsible for complete cancer regressions in two metastatic melanoma patients treated with a type of immunotherapy called adoptive T-cell therapy. This new approach may help develop more effective cancer immunotherapies, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

"This study provides the technical solution to identify mutated tumor targets that can stimulate immune responses, which is one of the major bottlenecks in developing a new generation of adoptive T-cell therapy," said Steven A. Rosenberg, MD, PhD, chief of surgery at the National Cancer Institute (NCI) in Bethesda, Maryland. "The two targets identified in this study play important roles in cancer cell proliferation.

"Immunotherapy has the potential to successfully treat cancer by targeting tumor mutations. We've moved one step closer because of this study," Rosenberg added.

Adoptive T-cell therapy is a type of immunotherapy in which the immune cells infiltrating a patient's tumor, so called tumor-infiltrating lymphocytes (TILs, which are T cells), are harvested, activated and expanded in the laboratory, and transferred back to the patient. Such activated cells are capable of efficiently attacking tumor cells.

"In a clinical trial, up to 72 percent of the patients with metastatic melanoma experienced tumor regression after adoptive T-cell transfer. However, not all patients benefited. This is because the specificity of the TILs remains largely unclear. Our goal was to establish an efficient method to identify the specificity of these cells," explained Rosenberg.

The researchers took tumor samples from two patients who had benefited from the therapy and pursued two screening approaches to identify the tumor targets recognized by the clinically effective T cells. First, they used a conventional screening method called cDNA library screening to identify nonmutated targets. Second, they used a novel method called tandem minigene library screening to identify mutated targets that cannot be found by the conventional method of screening.

For the second approach, the researchers used next-generation DNA sequencing to sequence the coding regions of the DNA from the two patients' tumors, and identified mutations. Next, they generated a library of these mutations. Instead of synthesizing the entire mutated gene, they synthesized only a small region surrounding the mutation (hence the name "minigene" library). They then screened the minigene library to identify those targets in the patients' tumors that were recognized by their TILs.

Using cDNA library screening, the researchers identified three novel nonmutated tumor targets, and four previously known non-mutated tumor targets.

Using tandem minigene library screening, they identified two novel mutated tumor targets, KIF2C and POLA2, which play important roles in cell proliferation.

With the minigene library approach, Rosenberg and colleagues recently reported another novel tumor target recognized by the activated T cells of a patient with bile duct cancer, who responded to adoptive T-cell transfer.

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Cancer mutations identified as targets of effective melanoma immunotherapy

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PUBLIC RELEASE DATE:

1-Jul-2014

Contact: Jeremy Moore jeremy.moore@aacr.org 215-446-7109 American Association for Cancer Research

PHILADELPHIA A new approach demonstrated that the recognition of unique cancer mutations appeared to be responsible for complete cancer regressions in two metastatic melanoma patients treated with a type of immunotherapy called adoptive T-cell therapy. This new approach may help develop more effective cancer immunotherapies, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

"This study provides the technical solution to identify mutated tumor targets that can stimulate immune responses, which is one of the major bottlenecks in developing a new generation of adoptive T-cell therapy," said Steven A. Rosenberg, MD, PhD, chief of surgery at the National Cancer Institute (NCI) in Bethesda, Maryland. "The two targets identified in this study play important roles in cancer cell proliferation.

"Immunotherapy has the potential to successfully treat cancer by targeting tumor mutations. We've moved one step closer because of this study," Rosenberg added.

Adoptive T-cell therapy is a type of immunotherapy in which the immune cells infiltrating a patient's tumor, so called tumor-infiltrating lymphocytes (TILs, which are T cells), are harvested, activated and expanded in the laboratory, and transferred back to the patient. Such activated cells are capable of efficiently attacking tumor cells.

"In a clinical trial, up to 72 percent of the patients with metastatic melanoma experienced tumor regression after adoptive T-cell transfer. However, not all patients benefited. This is because the specificity of the TILs remains largely unclear. Our goal was to establish an efficient method to identify the specificity of these cells," explained Rosenberg.

The researchers took tumor samples from two patients who had benefited from the therapy and pursued two screening approaches to identify the tumor targets recognized by the clinically effective T cells. First, they used a conventional screening method called cDNA library screening to identify nonmutated targets. Second, they used a novel method called tandem minigene library screening to identify mutated targets that cannot be found by the conventional method of screening.

For the second approach, the researchers used next-generation DNA sequencing to sequence the coding regions of the DNA from the two patients' tumors, and identified mutations. Next, they generated a library of these mutations. Instead of synthesizing the entire mutated gene, they synthesized only a small region surrounding the mutation (hence the name "minigene" library). They then screened the minigene library to identify those targets in the patients' tumors that were recognized by their TILs.

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New approach identifies cancer mutations as targets of effective melanoma immunotherapy

Recommendation and review posted by Bethany Smith

DALLAS, July 1, 2014 /PRNewswire/ --

The report "Cell Culture Marketby Equipment (Bioreactor, Incubator, Centrifuge), by Reagent (Media, Sera, Growth Factors, Serum Free Media), by Application (Cancer Research, Gene Therapy, Drug Development, Vaccine Production, Toxicity Testing) - Global Forecast to 2018" published by MarketsandMarkets, provides a detailed overview of the major drivers, restraints, challenges, opportunities, current market trends, and strategies impacting the global Cell Culture Market along with the estimates and forecasts of the revenue and market share analysis.

Browse 91 market data tables and 13 figures spread through 210 Pages and in-depth TOC on "Cell Culture Market"

http://www.marketsandmarkets.com/Market-Reports/cell-culture-market-me ...

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The global Cell Culture Market was valued at an estimated $14,772 million in 2013. This market is expected to grow at a CAGR of 10.71% between 2013 and 2018, to reach $24,574 million in 2018.

The Cell Culture Market is segmented on the basis of cell culture equipment and cell culture media, sera, and reagents. Each of these two market segments is further divided into multiple product segments and subsegments. The cell culture equipment market consists of five segments, namely, bio-safety cabinets, consumables, lab equipment, sterilization equipment, and storage equipment. Of these, the lab equipment product segment had the largest share of the cell culture equipment market in 2013, whereas the consumables product segment is expected to grow at the highest CAGR between 2013 and 2018. The subsegments of the lab equipment segment are cell counters, centrifuges fermentors & bioreactors, and incubators. The subsegments of the storage equipment segments are cryogenic storage and refrigerators and freezers.

The cell culture media, sera, and reagents market consists of six segments, namely, contamination detection kits, cryoprotective agents, lab reagents, media, serum, and other reagents. Of these, the serum product segment had the largest share of the cell culture media, sera, and reagents market in 2013, whereas the media product segment is expected to grow at the highest CAGR between 2013 and 2018. The subsegments of the lab reagents segment are balanced salt solutions, buffers and chemicals, cell dissociation reagents, and supplements and growth factors. The subsegments of the media segment are basal media, reduced serum media, and serum-free media.

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The application segments included in this report are biopharmaceutical production, cancer research, drug screening and development, gene therapy, tissue culture and engineering, toxicity testing, vaccine production, and other applications. The biopharmaceutical production application segment had the largest share of the cell culture equipment market in 2013, whereas the vaccine production application segment is expected to grow at the highest CAGR between 2013 and 2018. The geographic segments included in this report are North America, Europe, Asia-Pacific, and Rest of the World.

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Cell Culture Market worth $24,574 Million by 2018

Recommendation and review posted by Bethany Smith

PUBLIC RELEASE DATE:

1-Jul-2014

Contact: Jean Horrigan neinews@nei.nih.gov 301-496-5248 NIH/National Institute on Deafness and Other Communication Disorders

Researchers at the National Eye Institute (NEI) have described the functions of a gene responsible for anchoring cilia sensory hair-like extensions present on almost every cell of the body. They show in a mouse model that without the gene Cc2d2a, cilia throughout the body failed to grow, and the mice died during the embryonic stage. The finding adds to an expanding body of knowledge about ciliopathies, a class of genetic disorders that result from defects in the structure or function of cilia. NEI is part of the National Institutes of Health.

The findings are published in the online journal Nature Communications. Senior author Anand Swaroop, Ph.D., is chief of the NEI laboratory of Neurobiology-Neurodegeneration and Repair. Lead author Shobi Veleri, Ph.D., is a research fellow in the laboratory.

Cilia are responsible for cell communication and play a key role in the receptor cells of sensory systems. For example, they are essential for odor detection in the nose and light reception in the eye. Because cilia are such a key element of cells, defects in genes that are involved in cilia development or function can cause complicated syndromes involving multiple organs and tissues

Bardet-Biedl and Joubert syndromes are examples of ciliopathies with symptoms that include deafness, kidney disease, and degeneration of the retina. Meckel syndrome is a ciliopathy so dangerous babies with the genetic defect rarely make it to term.

On individual cells, cilia grow from the basal body, a circular dent on the outer membrane acting as a platform. Supporting structures called distal and subdistal appendages, which are like the flying buttresses supporting Notre Dame Cathedral, anchor the platform in the basal body, priming it for the growth of cilia. Once anchored, the structures that form the cilium begin to extend from the site. Inside are a variety of proteins essential to maintain the cilium. Cc2d2a is believed to make a structural protein needed for cilia growth, but its precise functions have been unclear.

Researchers developed a mouse lacking Cc2d2a to investigate the gene.

When they looked at the tissues of the mutant mice in very early stages of development, researchers found very few to no cilia, suggesting the gene plays a critical role at an early time. Looking closely at where the cilia should exist, the researchers saw that the supporting structures needed for cilia to grow were either completely missing or abnormal. In other experiments, the researchers found that the absence of Cc2d2a affected the activity of other genes and proteins involved in mouse nervous system development, including the key signaling protein, sonic hedgehog.

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NIH study reveals gene critical to the early development of cilia

Recommendation and review posted by Bethany Smith

Published: Wednesday, July 2, 2014 at 6:01 a.m. Last Modified: Tuesday, July 1, 2014 at 4:29 p.m.

Genetic engineering is such a polarizing topic that it is hard to have an even-handed debate of the issue.

Some opponents of genetically modified organisms, or GMOs, spread false claims about safety while ignoring the vast amount of research to the contrary.

That frustrates University of Florida researchers who have made advances in genetic engineering that might provide benefits in fighting crop diseases and reducing the need for pesticides if they could get beyond public misconceptions.

As The Sun reported this week, UF researchers have taken a gene found in bell peppers and transferred it to tomatoes. The process has made tomatoes that are resistant to a particularly troublesome crop disease and have a higher yield.

Contrary to scare stories about Frankenfoods, these methods represent a more technologically advanced way of doing the kind of crop breeding that has happen for millennia.

But Florida tomato growers worry they wouldn't be able to sell a GMO product, hampering the ability of researchers to attract investors.

"People are afraid, they don't understand why, they are just told they should be," Sam Hutton, a UF plant scientist involved in the research, told The Sun. "The anti-GMO crowd screams really loud, and there is a lot of fearmongering. It sounds bad to people who don't understand the science."

Other GMOs being developed at UF include a strawberry that can be grown without fungicides. A researcher involved in that effort told The Sun that the crop likely won't go beyond the lab without a change in public attitudes.

"You have solutions that can help the environment, help farmers and help people in the developing world, and you can't use it," said Ken Folta, professor and chairman of UF's Horticultural Sciences Department.

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Editorial: Fanning GMO fears

Recommendation and review posted by Bethany Smith