When two scientific papers, published in the journal Nature in January, described an inexpensive, uncontroversial and quick method of creating stem cells, it was hailed as a path-breaking discovery.

However, five months later, the research stands discredited after Nature retracted the papers Wednesday, and the study's inclusion in the prestigious journal has cast doubts on its peer-review process. In a retraction published by Nature, the researchers admitted that several critical errors had been found in the article, and that these multiple errors impair the credibility of the study as a whole.

In the research papers published in January, scientists from the Riken Centre for Developmental Biology in Japan had described a process to convert mature skin cells into pluripotent stem cells. Pluripotent stem cells are embryonic -- like stem cells that can be grown into any kind cell, tissue or organ. The method described in the papers was fairly straightforward and involved immersing the cells in an acid bath to create what the researchers called Stimulus Triggered Acquired Pluripotency Stem Cells, or STAP-SC.

Currently, there are only two ways to create stem cells. One involves extracting stem cells from the embryo, which results in its destruction and is therefore considered controversial. The other method requires the insertion of DNA into adult cells and is extremely expensive. Furthermore, the stem cells created through the second method are unstable and mostly unviable due to the presence of foreign genetic material.

Since the method described in the papers did not require the destruction of an embryo or the insertion of foreign DNA, it was heralded as a revolutionary new breakthrough in stem-cell technology. However, soon after the publication of the papers, a number of errors came to light.

One of the scientists involved in the research, Teruhiko Wakayama, also called for a retraction in March. This led to an internal investigation by the Riken Centre, which found in April that the studys lead author, Haruko Obokata, had misrepresented data in her research papers.

In an editorial accompanying the retraction published Wednesday, Nature stated that the all co-authors of both the papers had finally concluded that they cannot stand behind the papers, and have decided to retract them. The editorial also stated that the episode disclosed flaws in Natures procedures, and expressed the need to move quality assurance higher up on its agenda.

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"Acid Bath Stem Cell" Breakthrough Debunked, Nature Retracts Papers

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The POSITIVE project will focus on the development and establishment of a procedure to automate the first step of manufacturing of Ovasave, TxCells lead innovative, personalized cellular immunotherapy for severe refractory Crohns disease patients. Biosafes Sepax system will enable the automated and standardized separation of mononuclear white blood cells for the production of cellular immunotherapy.

This collaborative project, accredited by the French competitive cluster Eurobiomed, is supported by APRF funding (Appel Projet Recherche Finalise), from the Conseil Rgional Provence-Alpes-Cte-Dazur. The grant totals EUR 417,000, of which TxCell will receive a grant of EUR 250,000 and UTCG will receive EUR 167,000. Both grants will be for the performance of experiments by TxCell and UTCG and the optimization of the resulting new automated and standardized procedure. Biosafe will also utilise its Sepax technology expertise and know-how to optimize the dedicated software and protocol.

Participating in the POSITIVE project, and automating the TxCell manufacturing process for Ovasave is very important to us following the partnership with Ferring announced earlier this year with a potential value of EUR 76 million plus royalties, said Damian Marron, CEO, TxCell. Working with our highly qualified partners from UTCG and Biosafe, and backed by the Conseil Rgional Provence-Alpes-Cte-Dazur, Ovasave will be able to pave the way for scale up, industrialisation and commercialisation of cellular immunotherapies for TxCell, other biotech companies and public institutions. This is the next step following the announcement of our certification of GMP by the ANSM.

The process developed by the POSITIVE project will be applicable to a wide range of other cellular immunotherapies, allowing to overcome the constraints of manual methods and to move towards standardized large scale manufacturing in closed systems.

The industrialization of cellular immunotherapies is crucial for those operating in the sector as well as for TxCell, said Eric Pottier, VP Supply Chain at TxCell. New industrial tools are needed to enable commercial scale manufacturing. This could make cellular immunotherapies available to the large number of patients with a variety of conditions with unmet medical need that are waiting for innovative therapeutic options.

About TxCell

TxCell is developing innovative personalized cell-based immunotherapies for the treatment of severe chronic inflammatory diseases with high medical need using its unique and proprietary ASTrIA technology platform based on the properties of autologous antigen-specific regulatory T lymphocytes (Ag-Tregs). The company has completed a phase I/IIa study of its lead product candidate, Ovasave in refractory Crohns disease patients and has reported good tolerability and positive clinical efficacy. The company plans to initiate a phase IIb study in the same patient population. TxCell has a strategic partnership for Ovasave with the Swiss company Ferring International Center. Listed on Euronext-Paris, TxCell, a spin-off of Inserm (Frances National Institute for Health and Medical Research) is located in the Sophia Antipolis technology park, Nice, France. The company has 38 employees based at its headquarters and at its manufacturing site in Besanon.

For more information, please visitwww.txcell.com

Practical Information about TxCell shares: ISIN code FR0010127662 Ticker code TXCL

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July 3, 2014

redOrbit Staff & Wire Reports Your Universe Online

A gene acquired from an extinct cousin of modern humans is responsible for helping Tibetans adapt to high altitudes, according to new research published online by the weekly science journal Nature on Wednesday.

Scientists from the University of California, Berkeley and Chinese genomics organization BGI-Shenzen found that Tibetans acquired the ability when their ancestors mated with Denisovans or individuals related to the now-extinct species. This is said to be the first time that a gene originating from a different species has been essentially proven to have helped modern humans adapt to the environment around them.

The variant in question is involved with the regulation of hemoglobin production in the body, affecting the molecule that is responsible for transporting oxygen in the blood. It became widespread several thousands of years ago, when Tibetans first relocated to the high-altitude plateau, and has allowed them to survive at elevations of more than 15,000 feet, despite the lack of oxygen and the tendency for people to develop cardiovascular problems.

We have very clear evidence that this version of the gene came from Denisovans, a human relative that went extinct about the same time as Neanderthals, approximately 40,000 to 50,000 years ago, principal author and UC Berkeley integrative biology professor Rasmus Nielsen explained in a statement. This shows very clearly and directly that humans evolved and adapted to new environments by getting their genes from another species.

In their study, Nielsen and his colleagues re-sequenced the area surrounding EPAS1, a hypoxia pathway gene previously liked to differences in hemoglobin concentration at high altitude, in 40 Tibetan and 40 Han individuals. They discovered that, in Tibetans, the gene possessed a highly differentiated haplotype previously observed only in the Denisovan genome, one Southern Han Chinese individual, and one Beijing Han Chinese individual.

According to the researchers, EPAS1 is activated when oxygen levels in the blood decrease, and triggers the production of more hemoglobin. It has also been called the superathlete gene, because some variants of it can help athletes quickly boost the oxygen-carrying capacity of their blood at low altitudes, thus increasing their endurance.

However, at high altitudes, the common variants boost hemoglobin too much, increasing the bloods thickness and increasing the risk of high blood pressure, heart attack, low birth weight in babies, and higher infant mortality rates. The variant found in Tibetans, however, only increases hemoglobin levels slightly at higher elevations, meaning that they are immune to the side effects typically experienced by people at heights of over 13,000 feet.

The Denisovan-like DNA we found in the genome of Tibetans implied that the adaptation to local environments could be facilitated by gene-flow from other hominins who have been adapted to such environments, said BGI-Shenzen scientist Xin Jin. This unique finding may help us re-examine the similar fast-evolution cases in the future.

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ICGEB 19th symposium 2014
Photos from 19th symposium 2014.

By: International Centre for Genetic Engineering and Biotechnology

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Mysore, July 3, 2014, DHNS:

Rajya Sabha member Prof Rajiv Gowda onThursday asserted that there were many advantages to mankind through the study of genes.

Addressing the gathering of researchers at the opening of Know Your Genome, a laboratory, at RaniBahadurAuditorium in the city, Gowda said, the findings of genetic engineering was laudable, especially in protecting ones health.

However, there were also dangers of misusing the same, eventually leading to legal complications.

Though the study of genetics was exorbitant, there were still ways to reach the same to the common man.

Visiting Professor of IISc, Bangalore,HARanganath stressed that genetics studies be included in the syllabus to equip the students with the basics of the subject.

Ranganath exhorted the University of Mysore to start a department and research centre in genetics studies, to produce a pool of young experts. The lab

A dedicated laboratory was been opened in Vijayanagar in the city on Thursday.

The lab, Know your genome helps one ascertain the diseases he/she can be afflicted with in advance, and the required treatment.

According to its founderAvinash Veerappa, said that tests will be conducted in two levels by collecting samples of blood and mucus.

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Newswise (NEW YORK CITY July 3, 2014) Pediatric patients and their families recently joined physicians from The Icahn School of Medicine at Mount Sinai and representatives from the Genetic Disease Foundation (GDF) to introduce revamped quarters for the Food for Life program, which serves patients in Mount Sinais Program for Inherited Metabolic Diseases one of the largest centers of its kind. Food for Life was created to improve access to the specialized and often costly foods patients need to manage their health. Established with a grant from the GDF, the program features an on-site pantry stocked with food products made available at no cost to qualifying patients, along with advice and recipes from staff nutritionists.

Were extremely pleased to implement the Food for Life program with the GDFs support to help our patients, many of whom are children, overcome barriers to optimal health and well-being, said Melissa Wasserstein, MD, Associate Professor of Genetics and Genomics and Associate Professor of Pediatrics at the Icahn School of Medicine at Mount Sinai and Director of the Program for Inherited Metabolic Diseases. Enormous strides in research and biochemical genetics mean that once-fatal metabolic disorders, usually diagnosed at birth, can now be treated with life-long medical and nutritional management.

Inherited metabolic diseases are caused by genetic errors that result in enzyme deficiencies, which make it impossible for the body to properly process certain types of foods. Toxins build up in organs to cause debilitating and life-threatening effects. Treatments include medications and a medically-prescribed diet.

Because their diets are severely restricted, patients need to consume specially-manufactured formulas and other foodstuffs, Dr. Wasserstein explains. If they eat off-limit foods, they can have serious health repercussions, like neurological damage or even coma, depending on the disease.

GDF is honored to make the innovative Food for Life program possible, said Lorie Broser, GDF Board member. We hope this addition to the excellent care provided at Mount Sinais Department of Genetics & Genomic Sciences will make a positive difference for the patients and families.

The celebration centered around completion of a new interior wall design at the Food for Life reception area. To enhance the program experience for patients and families, GDF enlisted visionary designer Edin Rudic, who donated his time to create an inspiring atmosphere featuring an unusual blend of artistry, color and technology. The area now includes specially-coated walls on which kids can draw, and an HD screen to display photos from patients, some of whom were on hand for the event.

For more information or to make a donation, visit the Food for Life program online. And for digital video b-roll and interviews with program staff and patient families, visit http://www.youtube.com/watch?v=MeZKmvQUKME&feature=youtu.be.

About the Program for Inherited Metabolic Diseases The Program for Inherited Metabolic Diseases (PIMD) at the Mount Sinai Health System specializes in providing advanced clinical and diagnostic services for the treatment of more than 600 children and adults affected by inborn errors of metabolism. Complete diagnostic evaluations, comprehensive testing, interpretation of test results, and long-term medical and nutritional management are provided.

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Let #39;s Play The Sims 3 - Perfect Genetics Challenge: Cowgirl and Horse Edition Episode 12
Come join me on my latest journey into the complex world of sims 3 genetics, as I try to get perfect foals and perfect children. Will I succeed in getting perfect genetics in both? Can I keep...

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CONVERGE LIVE: Innovations in Population Health
Speaker: David Nash, M.D., Dean, Jefferson School of Population Health (@JeffersonJSPH) Join a special session broadcast live on MedCityNews.com and held in the exhibitor area of CONVERGE...

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Balancing Work Benefits after Spinal Cord Injury
Many people with spinal cord injuries want to work but worry about how their Social Security disability benefits will be affected. In this video, Emma Hensel...

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Shyamanga Borooah #39;s Three Minute Thesis - Developing a Clear Vision of the Future
Shyamanga Borooah from the MRC Centre for Regenerative Medicine in the College of Medicine and Veterinary Medicine presented his Three Minute Thesis entitled...

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By Steven Reinberg HealthDay Reporter

TUESDAY, July 1, 2014 (HealthDay News) -- A new bone marrow transplant technique for adults with sickle cell disease may "cure" many patients. And it avoids the toxic effects associated with long-term use of anti-rejection drugs, a new study suggests.

This experimental technique mixes stem cells from a sibling with the patient's own cells. Of 30 patients treated this way, many stopped using anti-rejection drugs within a year, and avoided serious side effects of transplants -- rejection and graft-versus-host disease, in which donor cells attack the recipient cells, the researchers said.

"We can successfully reverse sickle cell disease with a partial bone marrow transplant in very sick adult patients without the need for long-term medications," said researcher Dr. John Tisdale, a senior investigator at the U.S. National Heart, Lung, and Blood Institute.

In the United States, more than 90,000 people have sickle cell disease, a painful genetic disorder found mainly among blacks. Worldwide, millions of people have the disease.

Many adults with sickle cell disease have organ damage. This makes them ineligible for traditional transplants, which destroy all their bone marrow cells and use unmatched donor cells, he said. "Doing it this way would allow them access to a potential cure," Tisdale said.

"Adult patients, in whom symptoms are very severe, should consider whether a transplant could be right for them," he said. "A simple blood test for their siblings could tell them whether this approach is an option."

One expert was enthusiastic about the report, published July 2 in the Journal of the American Medical Association.

"The outcomes look every bit as good, if not better, than anything reported so far," said Dr. John DiPersio, chief of the division of oncology at Washington University School of Medicine in St. Louis.

"The issue is whether this can be extended to unrelated donors and to mismatched donors," said DiPersio, also the author of an accompanying journal editorial.

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A new study shows that adipose-derived human stem cells, which can become vital tissues such as bone, may be highly resistant to the common chemotherapy drug methotrexate (MTX). The preliminary finding from lab testing may prove significant because MTX causes bone tissue damage in many patients.

MTX is used to treat cancers including acute lymphoblastic leukemia, the most common form of childhood cancer. A major side effect of the therapy, however, is a loss of bone mineral density. Other bone building stem cells, such as bone marrow derived stem cells, have not withstood MTX doses well.

"Kids undergo chemotherapy at such an important time when they should be growing, but instead they are introduced to this very harsh environment where bone cells are damaged with these drugs," said Olivia Beane, a Brown University graduate student in the Center for Biomedical Engineering and lead author of the study. "That leads to major long-term side effects including osteoporosis and bone defects. If we found a stem cell that was resistant to the chemotherapeutic agent and could promote bone growth by becoming bone itself, then maybe they wouldn't have these issues."

Stem cell survivors

Originally Beane was doing much more basic research. She was looking for chemicals that could help purify adipose-derived stem cells (ASCs) from mixed cell cultures to encourage their proliferation. Among other things, she she tried chemotherapy drugs, figuring that maybe the ASCs would withstand a drug that other cells could not. The idea that this could help cancer patients did not come until later.

In the study published online in the journal Experimental Cell Research, Beane exposed pure human ASC cultures, "stromal vascular fraction" (SVF) tissue samples (which include several cell types including ASCs), and cultures of human fibroblast cells, to medically relevant concentrations of chemotherapy drugs for 24 hours. Then she measured how those cell populations fared over the next 10 days. She also measured the ability of MTX-exposed ASCs, both alone and in SVF, to proliferate and turn into other tissues.

Beane worked with co-authors fellow center member Eric Darling, the Manning Assistant Professor in the Department of Molecular Pharmacology, Physiology and Biotechnology, and research assistant Vera Fonseca.

They observed that three chemotherapy drugs -- cytarabine, etoposide, and vincristine -- decimated all three groups of cells, but in contrast to the fibroblast controls, the ASCs withstood a variety of doses of MTX exceptionally well (they resisted vincristine somewhat, too). MTX had little or no effect on ASC viability, cell division, senescence, or their ability to become bone, fat, or cartilage tissue when induced to do so.

The SVF tissue samples also withstood MTX doses well. That turns out to be significant, Darling said, because that's the kind of tissue that would actually be clinically useful if an ASC-based therapy were ever developed for cancer patients. Hypothetically, fresh SVF could be harvested from the fat of a donor, as it was for the study, and injected into bone tissue, delivering ASCs to the site.

To understand why the ASCs resist MTX, the researchers conducted further tests. MTX shuts down DNA biosynthesis by binding the protein dihydrofolate reductase so that it is unavailable to assist in that essential task. The testing showed that ASCs ramped up dihydrofolate reductase levels upon exposure to the drug, meaning they produced enough to overcome a clinically relevant dose of MTX.

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Stem cell type resists chemotherapy drug

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July 2, 2014

News Review From Harvard Medical School -- Transplant May Help Adults with Sickle Cell

A partial transplant of bone-marrow stem cells may reverse sickle cell disease in adults, a new study finds. People with sickle cell disease have abnormally shaped red blood cells. They get stuck in blood vessels. This causes organ damage, pain and other medical problems. The new study included 30 adults with severe sickle cell disease. Each of them had a brother or sister who was a suitable match for a bone-marrow stem cell transplant. The sibling donor's cells were mixed with some of the patient's own cells. During 3.4 years of follow-up, the partial transplant reversed sickle cell disease in 26 out of 30 people, researchers said. In these patients, the bone marrow began making normal red blood cells. Fifteen people also were able to stop taking drugs to prevent rejection of the transplant. Overall, people were much less likely than before to need hospital treatment for the disease. Use of narcotic drugs for pain also was greatly reduced. The Journal of the American Medical Association published the study. HealthDay News wrote about it July 1.

By Howard LeWine, M.D.Harvard Medical School

What Is the Doctor's Reaction?

In the United States, more than 90,000 people are affected by sickle cell disease. Most of them are African-American. Worldwide, the number is much higher. About 300,000 babies are born with this genetic disease every year.

In sickle cell disease, the red blood cells made in the bone marrow are abnormal. Instead of having a normal round shape, the cells are curved and stiff. This causes the red blood cells to get stuck inside blood vessels before they reach the tissues. The result:

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News Review From Harvard Medical School -- Transplant May Help Adults with Sickle Cell

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This image provided by the National Institutes of Health shows red blood cells in a patient with sickle cell disease at the National Institutes of Health Clinical Center in Bethesda, Md.AP Photo/National Institutes of Health

This image provided by the National Institutes of Health shows red blood cells in a different sickle cell patient, after a bone marrow transplant at the National Institutes of Health Clinical Center in Bethesda, Md.AP Photo/National Institutes of Health

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

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

The transplant worked in 26 of 30 adults, and 15 of them were even 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."

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, with hopes that 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.

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Last reviewed and revised on May 20, 2013

By Anthony L. Komaroff, M.D. Brigham and Women's Hospital

Both adult and umbilical cord stem cells already are used to treat disease.

Adult stem cells:

For many years, doctors have used adult stem cells successfully to treat human disease, through bone marrow transplantation (also known as hematopoietic stem cell transplantation). Most often, this treatment is used to treat cancers of the bloodlymphomas and leukemias. When all other treatments have failed, the only hope for a cure is to wipe out all of the patients blood cellsthe cancerous ones and the healthy onesand to give a patient an entirely new blood system. The only way to do this is to transplant blood stem cellscells that can reproduce themselves indefinitely and turn into all types of specialized blood cells.

Here's how it's done. First, the doctors need to collect blood stem cells from a patient's bone marrow, and let them multiply.

Second, the patient is given a dose of chemotherapy that kills all of the cancer cells a dose that, unfortunately, also kills the cells in the patient's bone marrow.

Third, the blood stem cellsthe cells designed to give the patient a whole new blood systemare given to the patient through an intravenous catheter. Hopefully, the blood stem cells then travel through the blood to the bone marrow, where they take up residence and start to make a new blood system.

Where do the blood stem cells come from? Most of the time, they come from the patient himself. They are sucked out of the patients bone marrow through a needle, or taken from the patients blood (some blood stem cells travel in the blood). So the blood stem cells are outside the patients body, growing in a laboratory dish, when the patient is given the chemotherapy that kills all the blood cells still inside the body.

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Special Harvard Commentary: How Stem Cells Help Treat Human Disease

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PUBLIC RELEASE DATE:

2-Jul-2014

Contact: Kristina Grifantini press@salk.edu Salk Institute

LA JOLLA-Researchers around the world have turned to stem cells, which have the potential to develop into any cell type in the body, for potential regenerative and disease therapeutics.

Now, for the first time, researchers at the Salk Institute, with collaborators from Oregon Health & Science University and the University of California, San Diego, have shown that stem cells created using two different methods are far from identical. The finding could lead to improved avenues for developing stem cell therapies as well as a better understanding of the basic biology of stem cells.

The researchers discovered that stem cells created by moving genetic material from a skin cell into an empty egg cell-rather than coaxing adult cells back to their embryonic state by artificially turning on a small number of genes-more closely resemble human embryonic stem cells, which are considered the gold standard in the field.

"These cells created using eggs' cytoplasm have fewer reprogramming issues, fewer alterations in gene expression levels and are closer to real embryonic stem cells," says co-senior author Joseph R. Ecker, professor and director of Salk's Genomic Analysis Laboratory and co-director of the Center of Excellence for Stem Cell Genomics. The results of the study were published today in Nature.

Human embryonic stem cells (hESCs) are directly pulled from unused embryos discarded from in-vitro fertilization, but ethical and logistical quandaries have restricted their access. In the United States, federal funds have limited the use of hESCs so researchers have turned to other methods to create stem cells. Most commonly, scientists create induced pluripotent stem (iPS) cells by starting with adult cells (often from the skin) and adding a mixture of genes that, when expressed, regress the cells to a pluripotent stem-cell state. Researchers can then coax the new stem cells to develop into cells that resemble those in the brain or in the heart, giving scientists a valuable model for studying human disease in the lab.

Over the past year, a team at OHSU built upon a technique called somatic cell nuclear transfer (the same that is used for cloning an organism, such as Dolly the sheep) to transplant the DNA-containing nucleus of a skin cell into an empty human egg, which then naturally matures into a group of stem cells.

Ecker, holder of the Salk International Council Chair in Genetics, teamed up with Shoukhrat Mitalipov, developer of the new technique and director of the Center for Embryonic Cell and Gene Therapy at OHSU, and UCSD assistant professor Louise Laurent to carry out the first direct comparison of the two approaches. The scientists created four lines of nuclear transfer stem cells all using eggs from a single donor, along with seven lines of iPS cells and two lines of the gold standard hESCs. All cell lines were shown to be able to develop into multiple cell types and had nearly identical DNA content contained within them.

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Newswise A team of researchers from the University of California, San Diego School of Medicine, Oregon Health & Science University (OHSU) and Salk Institute for Biological Studies has shown for the first time that stem cells created using different methods produce differing cells. The findings, published in the July 2, 2014 online issue of Nature, provide new insights into the basic biology of stem cells and could ultimately lead to improved stem cell therapies.

Capable of developing into any cell type, pluripotent stem cells offer great promise as the basis for emerging cell transplantation therapies that address a wide array of diseases and conditions, from diabetes and Alzheimers disease to cancer and spinal cord injuries. In theory, stem cells could be created and programmed to replace ailing or absent cells for every organ in the human body.

The gold standard is human embryonic stem cells (ES cells) cultured from discarded embryos generated by in vitro fertilization, but their use has long been limited by ethical and logistical considerations. Scientists have instead turned to two other methods to create stem cells: Somatic cell nuclear transfer (SCNT), in which genetic material from an adult cell is transferred into an empty egg cell, and induced pluripotent stem cells (iPS cells), in which adult cells are reverted back to a stem cell state by artificially turning on targeted genes.

Until now, no one had directly and closely compared the stem cells acquired using these two methods. The scientists found they produced measurably different results. The nuclear transfer ES cells are much more similar to real ES cells than the iPS cells, said co-senior author Louise Laurent, PhD, assistant professor in the Department of Reproductive Medicine at UC San Diego. They are more completely reprogrammed and have fewer alterations in gene expression and DNA methylation levels that are attributable to the reprogramming process itself.

The development and use of iPS cells has grown exponentially in recent years, in no small part due to the fact that they can be generated from adult cells (often from the skin) by temporarily turning on a combination of four genes to induce the adult cells to return to a pluripotent state.

Laurent noted that iPS cell lines have been created from patients to model many different diseases and the ability to make personalized iPS cells from a patient that could be transplanted back into that patient has generated excitement because it would eliminate the need for immunosuppression.

The nuclear transfer method has been pioneered more recently by a team led by Shoukhrat Mitalipov, PhD, professor and director of the Center for Embryonic Cell and Gene Therapy at OSHU. The technique is similar to the process used in cloning, but the pluripotent cells are collected from early embryos before they develop into mature organisms.

For their comparisons, the researchers at UC San Diego, OSHU and Salk created four nuclear transfer ES cell lines and seven iPS cell lines using the same skin cells as the source of donor genetic material, then compared them to two standard human ES lines. All 13 cell lines were shown to be pluripotent using a battery of standard tests.

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On a brilliant day in April, tens of thousands of baseball fans stream past Jonathan Thomas's office towards AT&T Park for the first home game of the San Francisco Giants 2014 season. Thomas's standing desk faces away from the window, but the cheering throngs are never far from his mind.

Thomas chairs the board of the California Institute for Regenerative Medicine (CIRM), the US$3-billion agency hailed by scientists around the world for setting a benchmark for stem-cell research funding. But scientists will not be the ones who decide what becomes of CIRM when the cash runs out in 2017. Instead, it will be the orange-and-black-clad masses walking past Thomas's window. And to win their support, Thomas knows that the agency needs to prove that their collective investment has been worthwhile. We need to drive as many projects to the patient as soon as possible, he says.

Californians voted CIRM into existence in 2004, making it the largest funder of stem-cell work in the world. The money the proceeds of bond sales that must be repaid with $3 billion in interest by taxpayers helped to bring 130 scientists to the state, and created several thousand jobs there. It has funded research that led to the publication of more than 1,700 papers, and it has contributed to five early clinical trials.

The institute has navigated a difficult path, however. CIRM had to revamp its structure and practices in response to complaints about inefficiency and potential conflicts of interest. It has also had to adapt its mission to seismic shifts in stem-cell science.

Now, ten years after taking off, the agency is fighting for its future. It has a new president, businessman Randal Mills, who replaces biologist Alan Trounson. Its backers have begun to chart a course for once again reaching out to voters, this time for $5 billion (with another $5 billion in interest) in 2016. And it is under intense pressure to produce results that truly matter to the public.

Whether or not CIRM succeeds, it will serve as a test bed for innovative approaches to funding. It could be a model for moving technologies to patients when conventional funding sources are not interested.

Much of what is celebrated and lamented about CIRM can be traced back to the Palo Alto real-estate developer who conceived of it: Robert Klein. Although officially retired from CIRM he chaired the board from 2004 to 2011 (see 'State of funding') Klein's office is adorned with mementos of the agency: a commemorative shovel from the groundbreaking of a CIRM-funded stem-cell research centre, and a photo of him with former governor Arnold Schwarzenegger at the ribbon-cutting ceremony.

Liz Hafalia/San Francisco Chronicle/Polaris/eyevine

Patient advocates and parents at a 2012 meeting in which US$100 million in CIRM grants were approved.

It was Klein's idea to ask voters to support stem-cell research in 2004, through a ballot measure called Proposition 71. When he succeeded, CIRM instilled a kind of euphoria in stem-cell scientists, who were at the time still reeling from a 2001 decree by then-President George W. Bush that severely limited federal funding for embryonic-stem-cell research. California's commitment removed this roadblock and revealed that many in the state and the country supported the research.

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Stem cells: Hope on the line

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Salk Institute scientist Joseph Ecker holds a flow cell slide used in a genome sequencing machine. Ecker and colleagues compared the genomes of two kinds of artificial embryonic stem cells for a study comparing their quality.

In a setback for hopes of therapy with a promising kind of artificial embryonic stem cells, a study published in the journal Nature has found that these "induced pluripotent stem cells" have serious quality issues.

However, scientists who performed the study, including researchers from the Salk Institute and UC San Diego, say it should be possible to improve the quality of these IPS cells. They say lessons can be learned from studying a newer technique of making human embryonic stem cells through nuclear transfer, the same technology used to create Dolly the cloned sheep.

In addition, the study does not prove that the quality problems will affect therapy with the cells, said scientists who examined the study. That remains to be tested.

The IPS cells are made from skin cells treated with "reprogramming" factors that turn back the clock, so they very closely resemble embryonic stem cells. The hope is that these IPS cells could be differentiated into cells that can repair injuries or relieve diseases. Because they can be made from a patient's own cells, the cells are genetically matched, reducing worries of immune rejection.

In San Diego, scientists led by Jeanne Loring at The Scripps Research Institute have created IPS cells from the skin cells of Parkinson's disease patients, and turned the IPS cells into neurons that produce dopamine. They hope to get approval next year to implant these cells into the patients, relieving symptoms for many years. The project is online under the name Summit4StemCell.org.

A major concern is that IPS cells display abnormal patterns of gene activation and repression. This is controlled by a process called methylation. This process adds chemicals called methyl groups to DNA, but these "epigenetic" changes do not change the underlying DNA sequence. Methylation represses gene function; removing the methyl groups, or demethylation, activates them.

The Nature study was led by Shoukhrat Mitalipov of Oregon Health & Scence University. Mitalipov made headlines last year for applying nuclear transfer to derive human embryonic stem cells, the first time this has been achieved in human cells. These cells can be made to be a near-perfect genetic match to the patient, and their quality closely resembles those of true embryonic stem cells.

"We know that the embryonic stem cells are the gold standard, and we've been always trying to make patient-matched cells that would match the gold standard," Mitalipov said. "And at this point it looks like the NT (nuclear transfer) cells produce exactly those cells that would be best."

Nuclear transfer involves placing a nucleus from a skin cell into an egg cell that has had its nucleus removed. The cell is then stimulated, and starts dividing in the same way a fertilized egg cell divides to form an embryo.

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Artificial embryonic stem cells have quality problems: study

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Dallas, TX (PRWEB) July 02, 2014

Cell Culture Market by 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 research report segments the cell culture market into two distinct market segments, namely, the cell culture equipment market and the cell culture media, sera, and reagents market. The segments of the cell culture equipment market included in this report are bio-safety cabinets, consumables, lab equipment, sterilization equipment, and storage equipment. The lab equipment segment consists of four subsegments, namely, cell counters, centrifuges, fermentors and bioreactors, and incubators. The storage equipment segment consists of two subsegments, namely, cryogenic storage and refrigerators and freezers.

The segments of the cell culture media, sera, and reagents market included in this report (http://www.lifescienceindustryresearch.com/cell-culture-market-by-equipment-bioreactor-incubator-centrifuge-by-reagent-media-sera-growth-factors-serum-free-media-by-application-cancer-research-gene-therapy-drug-development-vacci.html ) are contamination detection kits, cryoprotective agents, lab reagents, media, serum, and other reagents. The lab reagents segment consists of four subsegments, namely, balanced salt solutions, buffers and chemicals, cell dissociation reagents, and supplements and growth factors. The media segment consists of three subsegments, namely, basal media, reduced serum media, and serum-free media.

Cell culture has its applications in a large number of fields. On the basis of application, the report is segmented into biopharmaceutical production, cancer research, drug screening and development, gene therapy, tissue culture and engineering, toxicity testing, vaccine production, and other applications. The geographic segments included in this report are North America, Europe, Asia-Pacific, and Rest of the World.

The key drivers for this market are rapid increase in the demand for biopharmaceuticals and increased adoption of single-use technology. According to IMS Health, biopharmaceutical is expected to be the fastest growing pharmaceutical product segment by2017. Biopharmaceuticals are pharmaceutical products isolated from living organisms. Cell culture is one of the most important and widely used techniques for biopharmaceutical production. It was also the largest application segment of the cell culture market in 2013. Growth in the biopharmaceutical market will drive the growth of the cell culture market.

Companies profiled in this cell culture market research report include Becton, Dickinson and Company, Corning, Inc., Eppendorf AG, Lonza Group Ltd., Merck Kgaa, Sartorius AG, Sigma-Aldrich Corporation, Thermo Fisher Scientific, Inc. and Promocell GMBH. Order a copy of this report at http://www.lifescienceindustryresearch.com/purchase?rname=15929 .

Secondary information was used to identify the overall revenues, geographic reach, and product portfolios of the market players. Estimates of their cell culture segment revenues were validated through primary interviews. Primary interviews with key opinion leaders were also used to determine percentage shares of each subsegment and the relative differences in the growth rates.

The report provides qualitative insights about key market shares, growth rates, and market drivers for all important subsegments. It maps the market sizes and growth rates of each subsegment and identifies the segments poised for rapid growth in each of the geographic segments. The report also includes company profiles of the market leaders. These company profiles include financial performances, product portfolios, and market developments for each company. The report also provides a competitive landscape of the cell culture market. The competitive landscape covers the growth strategies adopted by the industry players over the last three years. It also includes analysis of industry developments like mergers and acquisitions, agreements and partnerships, and new product launches.

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The report will enable both established firms and new entrants to gauge the pulse of the market and help them make important strategic growth decisions. The report provides insights on the following:

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10.71% CAGR for Cell Culture Market Forecast to 2018 in a New Global Research Report Available at ...

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NEW YORKTibetans living on the roof of the world can thank an extinct human relative for providing a gene that helps them adapt to the high altitude, a study suggests.

Past research has concluded that a particular gene helps people live in the thin air of the Tibetan plateau. Now scientists report the Tibetan version of that gene is found in DNA from Denisovans, a poorly understood human relative more closely related to Neanderthals than modern people.

Denisovans are known only from fossils in a Siberian cave that are dated to about 50,000 years ago. Some of their DNA has also been found in other modern populations, indicating they interbred with ancient members of todays human race long ago.

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But the version of the high-altitude gene shared by Denisovans and Tibetans is found in virtually no other population today, researchers report in an article released Wednesday by the journal Nature.

That suggests that Denisovans or close relatives of theirs introduced the gene variant into the modern human species, but that it remained rare until some people started moving into the Tibetan plateau, said the studys main author, Rasmus Nielsen of the University of California, Berkeley.

At that point, it conferred a survival advantage and so spread through the Tibetan population, he said in an email. Its not clear whether the Denisovans were also adapted to high altitudes, he said.

The results show that as early members of todays human species expanded outside of Africa and encountered new environments, they could call on their genetic legacies from other species, he said. Thats easier than waiting for a helpful genetic mutation to arise, he said.

The Tibetan plateau rises above 4,000 metres in elevation. The genetic variant helps survival there by affecting the amount of oxygen the blood can carry when a person is in thin air. Apart from Tibetans, it is found very rarely in Han Chinese and also exists in Mongolians and Sherpas, Nielsen said. The researchers found no trace of it outside East Asia.

David Reich, an expert on ancient DNA at Harvard Medical School, called the paper important and exciting in showing the gene came from an ancient human relative. But he said that relative could have been Neanderthals, who are also known to have contributed DNA to modern people.

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Tibetans inherited high-altitude gene from extinct human relatives: study

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Mutation is similar to a 'super athlete' gene believed to give improved athletic performance Gene came from Denisovans, a human relative that became extinct 40,000-50,000 years ago Ethnic Tibetans split off from the Chinese Han less than 3,000 years ago

By Mark Prigg

Published: 16:16 EST, 2 July 2014 | Updated: 17:22 EST, 2 July 2014

Tibetans were able to adapt to high altitudes thanks to a gene picked up when their ancestors mated with a now extinct early species of human.

It is the first time a gene from another species of human has been shown unequivocally to have helped modern humans adapt to their environment, researchers said.

They found the gene came from Denisovans a human relative that became extinct 40,000-50,000 years ago, around the same time as the more well-known Neanderthals.

Tibetan nomads play billiards on an open grassland near Namtso Lake: Researchers have revealed the population evolved to thrive at high altitudes in just 3,000 years.

The gene has been referred to as the 'superathlete' gene because at low elevations, some variants of it help athletes quickly boost hemoglobin and thus the oxygen-carrying capacity of their blood, upping endurance.

At high altitudes, however, the common variants of the gene boost hemoglobin and its carrier, red blood cells, too much, increasing the thickness of the blood and leading to hypertension and heart attacks as well as low birth weight babies and increased infant mortality.

The variant, or allele, found in Tibetans raises hemoglobin and red blood cell levels only slightly at high elevations, avoiding the side effects seen in most people who relocate to elevations above 13,000 feet.

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'Super athlete' gene in Tibetans evolved in just 3,000 years

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This undated photo provided by BGI shows daily life in Tibet, an autonomous region of China. Tibetans can thank an extinct human relative for providing a gene that helps them adapt to the high altitude, according to a study released on Wednesday, July 2, 2014. (AP Photo/BGI)

NEW YORK -- Tibetans living on the "roof of the world" can thank an extinct human relative for providing a gene that helps them adapt to the high altitude, a study suggests.

Past research has concluded that a particular gene helps people live in the thin air of the Tibetan plateau. Now scientists report that the Tibetan version of that gene is found in DNA from Denisovans, a poorly understood human relative more closely related to Neanderthals than modern people.

Denisovans (de-NEE'-soh-vens) are known only from fossils in a Siberian cave that are dated to at least about 50,000 years ago. Some of their DNA has also been found in other modern populations, indicating they interbred with ancient members of today's human race long ago.

But the version of the high-altitude gene shared by Denisovans and Tibetans is found in virtually no other population today, researchers report in an article released Wednesday by the journal Nature.

That suggests that Denisovans or close relatives of theirs introduced the gene variant into the modern human species, but that it remained rare until some people started moving into the Tibetan plateau, said study main author Rasmus Nielsen of the University of California, Berkeley.

At that point, it conferred a survival advantage and so spread through the Tibetan population, he said in an email. It's not clear whether the Denisovans were also adapted to high altitudes, he said.

The results show that as early members of today's human species expanded outside of Africa and encountered new environments, they could call on their genetic legacies from other species, he said. That's easier than waiting for a helpful genetic mutation to arise, he said.

The Tibetan plateau rises above 13,000 feet in elevation. The genetic variant helps survival there by affecting the amount of oxygen the blood can carry when a person is in thin air.

FILE - In this June 11, 2008 file photo, Chinese Tibetan ethnic herdsmen try to catch a yak for sale in Dengsheng of Aba, China's southwest Sichuan province. Tibetans can thank an extinct human relative for providing a gene that helps them adapt to the high altitude, according to a study released on Wednesday, July 2, 2014. (AP Photo/Alexander F. Yuan, File)

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Ancient gene helps Tibetans cope with high altitude

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Tibetans, who thrive in an oxygen-scarce, high-altitude environment that leaves most gasping for breath, may have inherited their ability to adapt from an ancient human ancestor discovered just four years ago.

Earlier studies identified a version of a gene called EPAS1 as being responsible to Tibetans ability to adjust to their environment 4,000 meters (13,000 feet) above sea level. An analysis of the variant, which isnt found in other peoples, showed it in the remains of a Denisovan, the name for a species of human that lived about 41,000 years ago.

The findings, reported today in the journal Nature, suggest that interbreeding between modern humans and Denisovans provided the right genetic ingredients to enable their Tibetan descendants to thrive on the worlds highest plateau. In a broader sense, they also point to interbreeding between humans and other hominins as a key to survival in new environments.

Perhaps that process of adaptive introgression, of getting genes from other species, might be more important in evolution than previously thought, said Rasmus Nielsen, a professor at the University of California at Berkeley and one of the studys authors.

The Denisovans, a human species distinct from Neanderthals and modern humans, could have interbred with the ancestors of Tibetans before they migrated upwards, making the adaptations an essential advantage, Nielsen said.

The study focused on the EPAS1 gene because it regulates levels of oxygen-carrying hemoglobin. In most people, the gene causes the body to produce more hemoglobin when less oxygen is available. At high altitudes, it can go too far. Thickened blood can cause heart problems, hypertension and higher infant mortality.

The variation carried by Tibetans only raises hemoglobin production slightly, leading to a distinct survival advantage. The same high-altitude friendly variation was present in the genome sequenced from a single finger bone found in the Denisova Cave in southern Siberia. DNA sequencing in 2010 found that bone to be distinct from both Neanderthals and humans, which also inhabited the cave at different times. The full Denisovan genome was sequenced in 2012.

Studies have found humans probably interbred with Neanderthals and Denisovans before they became extinct. About 2 to 4 percent of human DNA today is made up of Neanderthal genes, according to research published earlier this year. Research has suggested the interbreeding may have conferred advantages enabling humans to survive in non-African environments.

The Tibetan adaptation strengthens the argument for adaptive introgression, in which advantageous genes are absorbed from existing populations, said Anna Di Rienzo, a professor of human genetics at the University of Chicago who has also researched the origin of the Tibetans genetic variation.

Its one of the most clear-cut cases of adaptive introgression with archaic humans, Di Rienzo said in an interview. Its clearly a very good case where we understand a lot about whats going on with this adaptation.

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Tibetans Got High-Altitude Gene From Archaic Humans

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Stephen Cass: Hello, Im Stephen Cass for IEEE Spectrums Techwise Conversations.

Nancy Kress is a celebrated author of science fiction and fantasy novels and short stories. First published in 1976, her work often focuses on the implications of genetic engineering and other biomedical technologies. Among other awards, she has won five Nebulas from the Science Fiction & Fantasy Writers of America.

As part of its 50th anniversary celebrations this August, Spectrum will be publishing Coming Soon Enough, an anthology of six original science fiction stories, including one by Kress titled Someone to Watch Over Me. But you dont have to wait to read it: The story is available now as part of Spectrums June special issue about the long-term future of technology.

Without giving anything away, Someone to Watch Over Me is a dark tale about the unintended consequences of advanced biomedical implant technology. To talk about the story and the broader themes that run throughout her work, Kress joins us now by phone from her home in Seattle. Nancy, welcome to the podcast.

Nancy Kress: Thank you. Im glad to be here.

Stephen Cass: So what was the inspiration for Someone to Watch Over Me?

Nancy Kress: I often write about children. The next generation of any society is, of course, what carries it forward. But in addition, we are faced right now with so many interesting possibilities, with genetic engineering and in other technologies as well, that the generation being born now is growing up far different than, say, the way I did. Texting, to me, would have seemed unimaginable. To them, its just normal ho-hum everyday kind of things. So when I was thinking about this story, I was thinking about cameraswhich, of course, are a far next generation of Google Glassthat actually fit in the eye and are not noticeable to anybody else or even possibly to the wearer, except in that they are recording. I naturally turn to the idea of a child wearing one, and I asked myself, What child? Under what circumstances? And from there the story grew. I frequently do start with a character.

Stephen Cass: So how closely do you then follow real-world technological developments? You mentioned Google Glass, which is an emerging technology

Nancy Kress: Im not trained as a scientist, which I deeply regret. When I was in high school, I didnt have chemistry because it conflicted with French 4, and now I cant do chemistry or speak French. It was a great tragedy. However, I try to keep up with the journals that are written for laymen, and when something captures my attention, Ill try to get the latest books on it. And I also collect microbiologists the way some people collect butterflies.

And I have a list of people that I can ask questions of when something captures my attention. So its kind of hit and miss whether some emergent technology comes to my attention. But if it does, and if it also succeeds in capturing that attention, then I try to find out about it in anyplace thats available to me.

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Nancy Kress: How Science Fiction Helps Us Rehearse for the Future

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