"Stress-Induced" Stem Cell Findings Are Retracted

High-profile reports claiming an easy way to create pluripotent cells were flawed.

The controversial work involved a mouse embryo injected with cells made pluripotent through stress. Credit: Haruko Obokata

Naturetoday retracted two controversial papers on stem cells that it published in January. The retractions agreed to by all of the co-authors come at the end of a whirlwind five months during which various errors were spotted in the papers, attempts to replicate the experiments failed, the lead author was found guilty of misconduct, and the centre where she is employed was threatened with dismantlement. The retraction noticeincludes a handful of problems with the papers that had not been previously considered by institutional investigation teams.

Questions remain over what exactly was the basis for claims that embryonic-like stem cells could be created by exposing bodily cells to stress a technology the authors called stimulus-triggered acquisition of pluripotency, orSTAP. But the controversy promises to have lasting impact on science in Japan, global stem-cell research, and the scientific community more broadly including changes in editorial policy at Nature. AnEditorial posted todaywith the retractions notes the need for improvements in publishing procedures: The episode has further highlighted flaws inNatures procedures and in the procedures of institutions that publish with us. (Natures news and comment team is editorially independent of its research editorial team.)

The first of the two papersdescribed a method of using acid exposure or physical pressure to convert spleen cells from newborn mice into pluripotent cells cells that can become any cell in the body. The second paperfurther impressed stem-cell scientists with data showing that the STAP process created cells that could differentiate into placenta cells, something that other pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, do not normally do.

But within weeks, duplicated and manipulated images were discovered, focusing attention on the source of data provided by Haruko Obokata, a biochemist at the RIKEN Center for Developmental Biology in Kobe and first author on both papers. Scientists also reported difficulties in replicating the experiments.

A RIKEN investigation team looking into the papers announced on April 1 that Obokata had been foundguilty of two counts of scientific misconduct. RIKENrejected an appeal, and advised her to retract the papers in May. Co-author Teruhiko Wakayama of the University of Yamanishi had been arguing for retraction since March.

Obokata and Charles Vacanti, an anaesthesiologist at the Brigham and Womens Hospital in Boston, Massachusetts, and the senior corresponding author on the first article, both stood by its claims, but later changed their positions after new errors emerged. Obokatagave her consent to the retraction of both paperson June 4.

The retraction notice published today lists five new errors. The first four note that captions do not describe what is in the corresponding images or figures, without reflecting on how this relates to the experimental data. The fifth, relating to the first paper, notes that purported STAP cells are of a different genetic background from those supposedly used in the experiments something it calls inexplicable discrepancies.

The notice concludes: These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC [stem cell] phenomenon is real.

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"Stress-Induced" Stem Cell Findings Are Retracted

Some stem cell methods closer to 'gold standard' than others

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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Some stem cell methods closer to 'gold standard' than others

Research integrity: Cell-induced stress

Kimimasa Mayama/EPA/Alamy

Haruko Obokata tearfully faces the media after she was found guilty of misconduct in April.

It seemed almost too good to be true and it was. Two papers1, 2 that offered a major breakthrough in stem-cell biology were retracted on 2 July, mired in a controversy that has damaged the reputation of several Japanese researchers.

For scientists worldwide it has triggered painful memories of a decade-old scandal. In February 2004, South Korean researcher WooSuk Hwang announced that he had generated stem-cell lines from cloned human embryos3, creating a potential source of versatile, therapeutic cells that would be genetically matched to any patient. A frenzy of excitement followed this and a subsequent publication4, but that didnt compare with the media firestorm when the results were revealed to be fabricated. The two main cloning papers were retracted5, and the careers of some dozen scientists were devastated.

In the soul-searching that followed, research integrity became a hot topic, scientists re-evaluated the responsibilities of authorship, and institutions vowed to improve the way that they police their staff. Nature and other journals also made promises, saying that they would vet manuscripts more thoroughly. In an Editorial at the time, Nature wrote6: Keeping in mind the principle that extraordinary claims require extraordinary proof, Nature may in rare cases demand it.

A year later, when Shoukhrat Mitalipov of the Oregon Health & Science University in Portland claimed to have cloned embryonic-stem-cell lines from monkeys7, Nature required independent tests to verify that the lines came from the monkey donors. This verification was published alongside the cloning paper8. I applaud what they did, says Alan Trounson, the outgoing president of the California Institute for Regenerative Medicine in San Francisco, who helped with the testing.

Then came Japans stem-cell case. This January, Haruko Obokata, a young biochemist at the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan, reported in Nature1, 2 that she had converted mouse cells to an embryonic-like state merely by subjecting them to stress, such as physical pressure or exposure to acid (see Nature 505, 596; 2014). The process, labelled stimulus-triggered acquisition of pluripotency (STAP), was so contrary to current thinking that some scientists said they accepted it based only on the reputation of Obokatas co-authors, who were some of the most trusted names in stem-cell research and cloning.

But the paper1 that set out the fundamental technique was soon shot full of holes. There was plagiarized text in the article. Figures showed signs of manipulation, and some images were identical or nearly identical to those used later in the same paper and elsewhere to represent different experiments. More damning were genetic analyses that strongly suggested the cells were not what they were purported to be. And although deriving STAP cells was advertised as simple and straightforward, no one has yet been able to repeat the experiment.

Within the space of six months, Obokata was found guilty of misconduct by her institution; well-respected scientists, including RIKEN head Ryoji Noyori, bowed their heads in apology; and both papers were retracted9. In the end, the evidence for STAP cells seemed so flimsy that observers began to ask where were the extra precautions and the extraordinary proof that had been promised post-Hwang.

The case has reopened difficult questions about the quality of research and peer review, and the responsibilities of co-authors, institutions and journals. It is also making its mark as an example of how not to do things. The episode has already become a parable in my lab for teaching students about scientific ethics, says Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California.

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Research integrity: Cell-induced stress

Artificial embryonic stem cells have quality problems: study

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

Adults stop anti-rejection drugs after stem-cell transplant reverses sickle cell disease

PUBLIC RELEASE DATE:

1-Jul-2014

Contact: Krysten Carrera NIDDKMedia@mail.nih.gov 301-496-3583 NIH/National Institute of Diabetes and Digestive and Kidney Diseases

Adults stop anti-rejection drugs after stem-cell transplant reverses sickle cell disease NIH trial success suggests a new treatment option for older, sicker patients

Half of patients in a trial have safely stopped immunosuppressant medication following a modified blood stem-cell transplant for severe sickle cell disease, according to a study in the July 1 issue of the Journal of the American Medical Association. The trial was conducted at the National Institutes of Health's Clinical Center in Bethesda, Maryland, by researchers from NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute.

The transplant done in the study reversed sickle cell disease in nearly all the patients. Despite having both donor stem-cells and their own cells in their blood, the patients stopped the immunosuppressant medication without experiencing rejection or graft-versus-host disease, in which donor cells attack the recipient. Both are common, serious side effects of transplants.

"Typically, stem-cell recipients must take immunosuppressants all their lives," said Matthew Hsieh, M.D., lead author on the paper and staff clinician at NIH. "That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen."

In sickle cell disease (SCD) sickle-shaped cells block blood flow. It can cause severe pain, organ damage and stroke. The only cure is a blood stem-cell, or bone marrow, transplant. The partial transplant performed in the study is much less toxic than the standard "full" transplant, which uses high doses of chemotherapy to kill all of the patient's marrow before replacing it with donor marrow. Several patients in the study had less than half of their marrow replaced.

Immunosuppressant medication reduces immune system strength and can cause serious side effects such as infection and joint swelling. In this study, 15 of 30 adults stopped taking the medication under careful supervision one year after transplant and still had not experienced rejection or graft-versus-host disease at a median follow up of 3.4 years.

"Side effects caused by immunosuppressants can endanger patients already weakened by years of organ damage from sickle cell disease," said John F. Tisdale, M.D., the paper's senior author and a senior investigator at NIH. "Not having to permanently rely on this medication, along with use of the relatively less-toxic partial stem-cell transplant, means that even older patients and those with severe sickle cell disease may be able to reverse their condition."

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Adults stop anti-rejection drugs after stem-cell transplant reverses sickle cell disease

Papers on stress-induced stem cells are retracted

Asahi Shimbun/Getty Images

Haruko Obokata, here at a 9 April news conference in Osaka, Japan, was found guilty of misconduct but stands by her claim of having produced stem cells by a novel procedure.

Nature today retracted two controversial papers on stem cells that it published in January1, 2. The retractions agreed to by all of the co-authors come at the end of a whirlwind five months during which various errors were spotted in the papers, attempts to replicate the experiments failed, the lead author was found guilty of misconduct, and the centre where she is employed was threatened with dismantlement. The retraction notice3 includes a handful of problems with the papers that had not been previously considered by institutional investigation teams.

Questions remain over what exactly was the basis for claims that embryonic-like stem cells could be created by exposing bodily cells to stress a technology the authors called stimulus-triggered acquisition of pluripotency, or STAP. But the controversy promises to have lasting impact on science in Japan, global stem-cell research, and the scientific community more broadly including changes in editorial policy at Nature. An Editorial posted today with the retractions notes the need for improvements in publishing procedures: The episode has further highlighted flaws in Natures procedures and in the procedures of institutions that publish with us. (Natures news and comment team is editorially independent of its research editorial team.)

The first of the two papers1 described a method of using acid exposure or physical pressure to convert spleen cells from newborn mice into pluripotent cells cells that can become any cell in the body. The second paper2 further impressed stem-cell scientists with data showing that the STAP process created cells that could differentiate into placenta cells, something that other pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, do not normally do.

But within weeks, duplicated and manipulated images were discovered, focusing attention on the source of data provided by Haruko Obokata, a biochemist at the RIKEN Center for Developmental Biology in Kobe and first author on both papers. Scientists also reported difficulties in replicating the experiments.

A RIKEN investigation team looking into the papers announced on 1 April that Obokata had been found guilty of two counts of scientific misconduct. RIKEN rejected an appeal, and advised her to retract the papers in May. Co-author Teruhiko Wakayama of the University of Yamanishi had been arguing for retraction since March.

Obokata and Charles Vacanti, an anaesthesiologist at the Brigham and Womens Hospital in Boston, Massachusetts, and the senior corresponding author on the first article, both stood by its claims, but later changed their positions after new errors emerged. Obokata gave her consent to the retraction of both papers on 4 June.

The retraction notice published today lists five new errors. The first four note that captions do not describe what is in the corresponding images or figures, without reflecting on how this relates to the experimental data. The fifth, relating to the first paper1, notes that purported STAP cells are of a different genetic background from those supposedly used in the experiments something it calls inexplicable discrepancies.

The notice concludes: These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC [stem cell] phenomenon is real.

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Papers on stress-induced stem cells are retracted

UVA Expands Cancer Treatment

UVA joins National Marrow Donor Program giving greater access to cancer treatments by Ishaan Sachdeva | Jun 25 2014 | 06/25/14 10:11pm | Updated 19 hours ago

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

Stem cells may be more widespread and with greater potential than previously believed

PUBLIC RELEASE DATE:

30-Jun-2014

Contact: Cody Mooneyhan cmooneyhan@faseb.org 301-634-7104 Federation of American Societies for Experimental Biology

With the plethora of research and published studies on stem cells over the last decade, many would say that the definition of stem cells is well established and commonly agreed upon. However, a new review article appearing in the July 2014 issue of The FASEB Journal , suggests that scientists have only scratched the surface of understanding the nature, physiology and location of these cells. Specifically, the report suggests that embryonic and induced pluripotent stem cells may not be the only source from which all three germ layers in the human body (nerves, liver or heart and blood vessels) can develop. The review article suggests that adult pluripotent stem cells are located throughout the body and are able to become every tissue, provided these cells receive the right instructions.

"This study highlights the mutual role of stem cells both for regeneration and in tumor growth by featuring two sides of the same coin: stems cells in cancer and regenerative medicine," said Eckhard Alt, M.D., Ph.D., the article's lead author from the Center for Stem Cell and Developmental Biology at the University of Texas MD Anderson Cancer Center in Houston, Texas. "Our workprovides novel insight on why and how mature has provided us with one universal type of stem cell that is equally distributed throughout the whole body, every organ and every tissue. Small early pluripotent stem cells are ubiquitously located in and around the blood vessels throughout the whole body and serve as a reserve army for regeneration."

In the review, Alt and colleagues suggest that small early pluripotent stem cells are able to replace any kind of tissue in the body--independent of where they comes from in the body--given that these cells receive the correct instructions. When researchers extract these cells from fat tissue, concentrated them and then injected them into diseased or injured tissue, they delivered beneficial outcomes for ailments such as heart failure, osteoarthritis, non-healing wounds, soft tissue defects, muscle, bone and tendon injuries and neurodegenerative diseases. The review also discusses how this is basically the same process that occurs in tumors, except that instead of healing or regenerating tissue, the cells work toward building a tumor. Better understanding and manipulating how these cells communicate not only will open new therapies that heal injury (heart failure, wounds, etc.), but will allow researchers to stop many cancers before they become life-threatening.

"This article suggests that the countless hours spent researching cancer and progenitor cells are finally coming to a head," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "As the intersection between cancer and stem cell research becomes closer and clearer, all of today's medical treatments will begin to look as crude as Civil War medicine."

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Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is among the most cited biology journals worldwide according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century.

FASEB is composed of 26 societies with more than 120,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

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Stem cells may be more widespread and with greater potential than previously believed

Thermo Fisher Showcases New Product Innovations and Best Practices to Optimize Stem Cell Discoveries at ISSCR 2014

VANCOUVER, British Columbia--(BUSINESS WIRE)--The latest advances in innovative technologies designed to streamline the entire stem cell research workflow from pluripotent cell engineering, culturing, differentiation and characterization to cryopreservation and storage will be showcased this week during the 12thannual International Society for Stem Cell Research (ISSCR) meeting (Thermo Scientific booth #628, Life Technologies booth #829).

Thermo Fisher Scientific will host a series of customer and thought leader presentations on topics ranging from the use of Sendai virus reprogramming technology for rapid development of human induced pluripotent stem cells (iPSC) for drug development applications, to industrializing pluripotent stem cells and novel platforms for culturing cells in suspension. The speakers will share new innovations being applied in labs at Harvard University, Cedar-Sinai Medical Center and Saitama Medical University.

Access to leading-edge tools that are designed to seamlessly work in combination with each other is critical for our customers to drive new discoveries, said Chris Armstrong, Ph.D., vice president and general manager, cell biology, for Thermo Fisher. Were proud to offer a deep portfolio of technologies that addresses the entire pluripotent stem cell research continuum to enable novel applications in drug discovery and human disease studies.

New product innovations at ISSCR this year include:

Thought Leader Presentations Join fellow ISSCR attendees for sponsored presentations, including: Wednesday, June 18, from 8:30 a.m. 12:30 p.m. (West Ballroom C/D): Conquering Roadblocks Associated with Stem Cell Differentiation and Disease Modeling:

Thursday, June 19, from 11:30 a.m. 12:30 p.m. (West Meeting Room) ISSCR Innovation Showcase

For more information on all Thermo Fisher activities during ISSCR, please visit Thermo Scientific ISSCR 2014 and Life Technologies ISSCR 2014.

About Thermo Fisher Scientific

Thermo Fisher Scientific Inc. is the world leader in serving science, with revenues of $17 billion and 50,000 employees in 50 countries. Our mission is to enable our customers to make the world healthier, cleaner and safer. We help our customers accelerate life sciences research, solve complex analytical challenges, improve patient diagnostics and increase laboratory productivity. Through our four premier brands Thermo Scientific, Life Technologies, Fisher Scientific and Unity Lab Services we offer an unmatched combination of innovative technologies, purchasing convenience and comprehensive support. For more information, please visitwww.thermofisher.com.

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Thermo Fisher Showcases New Product Innovations and Best Practices to Optimize Stem Cell Discoveries at ISSCR 2014

The Adult Stem Cell Technology Center, LLC Announces Patent for Induced Pluripotent Stem Cells Produced with a Single …

Valencia, Spain (PRWEB) June 24, 2014

Today at Cell Science-2014 in Valencia, Spain, Dr. James L. Sherley, Director of Bostons Adult Stem Cell Technology Center, LLC, announced the issue of another significant patent to the companys growing portfolio of adult tissue stem cell intellectual property. The new patent issued today (U.S. Patent and Trademark Office No. 8,759,098) protects a method for producing induced pluripotent stem cells (iPSCs) with a single non-genetic agent.

Director Sherley made the announcement at the conclusion of his keynote address at the 4th Annual World Congress on Cell Science and Stem Cell Research. After discussing unique aspects of adult stem cells that are often overlooked, he highlighted a proposed connection between adult stem cells and iPSCs that was the basis for the newly patented biotechnology.

iPSCs are currently the subject of intense biological and biomedical research. These artificially produced stem cells provide the research capabilities of human embryonic stem cells (hESCs). But since their production does not involve human embryos, iPSCs do not pose ethical concerns. However, because of their genetic defects and propensity for forming tumors, also like hESCs, it is unlikely that iPSCs will ever be of sufficient quality and safety for use in regenerative medicine therapies.

Despite the problems preventing direct application of iPSCs for medical therapies, their use to develop biological surrogate cells for difficult-to-obtain cells for diseased human tissues for research is unparalleled (e.g., living brain cells from children with autism). For this reason, new technologies, like those represented by the ASCTCs new patent, are important for leading the way to more efficient production of higher quality iPSCs.

Unlike the recently discredited reports of acidic conditions as a single non-genetic agent for producing iPSCs, the ASCTCs technology has a well-established historical record and biological rationale. The method was originally proposed in the National Institutes of Health (NIH) Directors Pioneer Award research of ASCTC Director Sherley, when he was a research professor at the Massachusetts Institute of Technology.

The active agent, xanthine, is a naturally occurring normal compound found in the bodys blood and tissues. In earlier ASCTC studies, xanthine was shown active for expanding adult tissue stem cells. Xanthine is a member of a class of compounds called purines that regulate the action of a well-known cancer-protective gene called p53. The p53 gene has also been shown by several laboratories to be an important factor in the efficiency of iPSC cell production.

For the ASCTC technology, xanthine-expanded adult tissue stem cells are placed in commonly used iPSC culture medium supplemented with xanthine as the only additive. The usual introduction of specific genes or their experimental manipulation is not required. The new single-agent technology yields iPSCs at efficiencies similar to methods that require direct genetic manipulation.

The ASCTCs iPSC production technology was described in an earlier issue of the Journal of Biomedicine and Biotechnology (Par, J.-F., and Sherley, J. L. 2011. Culture Environment-Induced Pluripotency of SACK-Expanded Tissue Stem Cells, J. Biomed. Biotechnol. vol. 2011, Article ID 312457, 12 pp., 2011. doi:10.1155/2011/312457). Thus far, the method has only been applied to purine-expanded mouse pancreatic tissue stem cells. It also has not been evaluated for combined effects with other iPSC production methods. Director Sherley notes that, wider evaluation of the new technology will help to establish its range as an advantageous new reagent for producing higher quality iPSCs more efficiently.

************************************************************************************************************* The Adult Stem Cell Technology Center, LLC (ASCTC) is a Massachusetts life sciences company established in September 2013. ASCTC director and founder, James L. Sherley, M.D., Ph.D. is the foremost authority on the unique properties of adult stem cells. The companys patent portfolio contains biotechnologies that solve the two main technical problems production and quantification that have stood in the way of successful commercialization of human adult tissue stem cells for cell medicine and drug development. Currently, ASCTC is employing its technological advantage to pursue commercialization of mass-produced therapeutic human liver cells and facile assays for screening-out drug candidates that are toxic to adult tissue stem cells.

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The Adult Stem Cell Technology Center, LLC Announces Patent for Induced Pluripotent Stem Cells Produced with a Single ...