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HEXIM1 regulatory protein induces human pluripotent stem cells to adopt more specialized cell fate

5 hours ago Human pluripotent stem cells, such as human embryonic stem cells (above), can differentiate into specific cell types under appropriate conditions; the HEXIM1 protein helps with this differentiation. Credit: DAJ/amana images/Thinkstock

A lot of optimism and promise surrounds the use of human pluripotent stem cells (hPSCs)for applications in regenerative medicine and drug discovery. However, technical challenges still hamper the culturing and differentiation of these cells, which include the cell types known as human embryonic stem cells (hESCs) and their reprogrammed equivalents, induced pluripotent stem cells (iPSCs).

A team of A*STAR scientists has now discovered a regulatory protein that helps to coax human pluripotent stem cells to form more specialized types of cells. "Our finding could help to develop a new protocol to induce differentiation of human pluripotent stem cells," says Sheng-Hao Chao from the A*STAR Bioprocessing Technology Institute (BTI) in Singapore, who led the study.

Chao and his co-workers at the BTI's Expression Engineering Group have been studying a protein called hexamethylene bisacetamide-inducible protein 1 (HEXIM1) for many years. HEXIM1 is known to inhibit a protein complex called positive transcription elongation factor b (P-TEFb), which is involved in gene expression. Chao's team previously linked HEXIM1 with a specific pathway involved in cancer development. This led the researchers to suspect an additional role for HEXIM1 in regulating stem cells.

Chao's group teamed up with Andre Choo and his colleagues in the Stem Cell Group at the BTI to further explore this possibility. They first treated hESCs with a differentiation-inducing compound called LY294002 and saw a marked increase in HEXIM1 levels compared to untreated cells.

Further tests showed that HEXIM1 played a role in driving cellular differentiation. For example, the hESCs differentiated when the researchers incubated the cells with hexamethylene bisacetamide (HMBA), a HEXIM1 inducing reagent, or when they generated and cultured a cell line with elevated expression of HEXIM1. The researchers rule out P-TEFb inhibition as an explanation for the effect, however, because in another experiment, hESCs treated with flavopiridola drug that blocks P-TEFb activityremained in a pluripotent state.

"We discovered a novel function of HEXIM1 in regulating the early-stage differentiation of human pluripotent stem cells through a P-TEFb-independent pathway," says Chao. More work is still needed to investigate in detail the molecular mechanism by which HEXIM1 drives hPSC differentiation.

Eventually, HEXIM1 could become a useful tool in generating new tissues for cell-replacement therapies. "In combination with other transcription factors or chemicals, it is possible that HEXIM1 and its inducing reagent HMBA could be utilized to direct the differentiation of human pluripotent stem cellsinto specific cell types," Chao says.

Explore further: Scientists engineer human stem cells

More information: Ding, V., Lew, Q. J., Chu, K. L., Natarajan, S., Rajasegaran, V. et al. "HEXIM1 induces differentiation of human pluripotent stem cells." PLoS ONE 8, e72823 (2013). dx.doi.org/10.1371/journal.pone.0072823

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HEXIM1 regulatory protein induces human pluripotent stem cells to adopt more specialized cell fate

Stem Cell Therapy – Facet Syndrome Patients Relieve Back and Neck Pain Dr Robert Wagner – NSPC – Video


Stem Cell Therapy - Facet Syndrome Patients Relieve Back and Neck Pain Dr Robert Wagner - NSPC
How to know if the cause of your back or neck pain is Facet Syndrome. Discover how biologic regenerative treatments are able to pick up where traditional tre...

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Stem Cell Therapy - Facet Syndrome Patients Relieve Back and Neck Pain Dr Robert Wagner - NSPC - Video

Foetal stem cell treatment sees success in fighting brittle bone disease Channel NewsAsia – Video


Foetal stem cell treatment sees success in fighting brittle bone disease Channel NewsAsia
A team of experts from Singapore #39;s National University Hospital (NUH) has made a clinical breakthrough in their work on foetal stem cell treatment, after suc...

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Foetal stem cell treatment sees success in fighting brittle bone disease Channel NewsAsia - Video

Stem Cell Therapy by Vet-Stem, a Surprising Alternative to Hip Surgery for a New Jersey Chocolate Labrador Retriever

Poway, CA (PRWEB) December 19, 2013

Amazing Grace Hamiltons banked stem cells from Vet-Stem, Inc. have recently helped her avoid hip surgery for the second time. Gracie is now nearly 12 years old and her owners noticed her activities had dramatically slowed in the last year. They turned to banked stem cells that Gracie had stored with Vet-Stem, Inc. in Poway, California to help with the discomfort and pain of arthritis that was slowing her down.

When Gracies owners brought her to Garden State Veterinary Specialists in Tinton Falls, New Jersey in October of this year the x-rays showed a severely deteriorated right hip. Dr. Thomas Scavelli and Dr. Michael Hoelzler were very concerned and recommended hip replacement. Gracies owners wanted to try stem cell therapy first, since it had given them such positive results five years before.

We needed to give the stem cells a try before going to the more invasive surgical approach, Mrs. Hamilton said. At the time of the procedure Dr. Hoelzler told me that Gracies hips were the worst he had seen, but in just a couple of days after the stem cell therapy we began to see a difference. Just shy of two weeks after the procedure I took her back to Dr. Hoelzler and he was very impressed. She was walking comfortably.

At three years Gracie had been diagnosed with hip dysplasia. By six years of age she had slowed to the point of great concern as her owners described it. The pain caused by arthritis from the hip dysplasia was beginning to interfere with her life.

Gracie was no longer running and jumping, and certain activities had become difficult (like climbing onto my husbands sailboat). She also had a noticeable limp, Mrs. Hamilton remembered the signs of pain and discomfort that prompted Gracies first stem cell therapy five years before.

Gracie was brought to Dr. Scavelli in 2008 with painful symptoms, and stem cell therapy for pets was the latest, cutting edge treatment. Gracies owners understood that without stem cell therapy Gracie would have faced hip surgery at the time.

We are grateful for stem cell therapy which has restored Gracies ability to enjoy her morning walks again, Mrs. Hamilton shared, She enjoys wrestling with us and playing with her toys. She looks forward to visiting her friends, and prances around like a puppy. Gracie is a happy dog and we are happy owners because she does not appear to be in pain anymore!

About Vet-Stem, Inc.

Vet-Stem, Inc. was formed in 2002 to bring regenerative medicine to the veterinary profession. The privately held company is working to develop therapies in veterinary medicine that apply regenerative technologies while utilizing the natural healing properties inherent in all animals. As the first company in the United States to provide an adipose-derived stem cell service to veterinarians for their patients, Vet-Stem, Inc. pioneered the use of regenerative stem cells in veterinary medicine. The company holds exclusive licenses to over 50 patents including world-wide veterinary rights for use of adipose derived stem cells. In the last decade over 10,000 animals have been treated using Vet-Stem, Inc.s services, and Vet-Stem is actively investigating stem cell therapy for immune-mediated and inflammatory disease, as well as organ disease and failure. For more on Vet-Stem, Inc. and Veterinary Regenerative Medicine visit http://www.vet-stem.com or call 858-748-2004.

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Stem Cell Therapy by Vet-Stem, a Surprising Alternative to Hip Surgery for a New Jersey Chocolate Labrador Retriever

UC Davis Institute for Regenerative Cures – UC Davis Health System

For patients and families suffering from chronic disease or injury, the promise of stem cell therapies offers great hope. UC Davis is a leader in advancing that promising goal. It has brought together physicians, research scientists, biomedical engineers and a range of other experts and collaborative partners to establish the UC Davis Institute for Regenerative Cures, a facility supported by the California Institute for Regenerative Medicine.

The new $62 million institute is located on the universitys Sacramento campus, where collaborative, team-oriented science is working to advance breakthrough discoveries and bring stem cell therapies and cures to patients everywhere. It benefits from being on a campus near a nationally-designated cancer center, a renowned neurodevelopmental institute, state-of-the-art imaging and biophotonics programs, and an academic medical center that is at the forefront of advanced patient care. The UC Davis School of Veterinary Medicine and the California National Primate Research Center, both of which are in nearby Davis, also offer unique research benefits for UC Davis scientists.

The institutes facilities include primary laboratories, a shared-vector core, microscopy and cell sorters, space for academic, postdoctoral and administrative offices, along with conference rooms and a proposed lecture hall.

The institute also is home to one of the largest, most advanced, academic Good Manufacturing Practice (GMP) facilities in the nation. With approximately 7,000 square feet of space, this GMP laboratory contains a suite of six specially designed rooms that enable researchers to safely process cellular and gene therapies for clinical trials. The facility is used by both UC Davis researchers and stem cell investigators from throughout the state and beyond.

Institute Goals

The UC Davis stem cell program brings together resources from across the university to ensure that bench research the work done in laboratories can be translated successfully into clinical treatments.

With an ability to repair damaged tissue and develop into specialized cells and organs, stem cells will have a major impact in medicine and health care. Research into stem and progenitor cell therapies is in full motion throughout the university. Scientists are exploring and testing different techniques and approaches in laboratories so that new and safe therapies are available to patients. This translation of basic scientific discoveries into novel therapies and clinical practices is a hallmark of research at UC Davis

Disease Teams

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UC Davis Institute for Regenerative Cures - UC Davis Health System

Adult Stem Cells Found to Suppress Cancer While Dormant

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Newswise Researchers at UCLAs Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have discovered a mechanism in adult stem cells by which the cells suppress their ability to initiate cancer during their dormant phase, an understanding that could be exploited for better cancer prevention strategies. The study was led by Andrew White, post-doctoral fellow, and William Lowry, associate professor of molecular, cell and developmental biology in the life sciences and the Maria Rowena Ross Term Chair in Cell Biology.

The study was published online ahead of print in Nature Cell Biology on December 15, 2013.

Hair follicle stem cells (HFSC), the tissue-specific adult stem cells that generate the hair follicles, are also the cells of origin for cutaneous squamous cell carcinoma (SCC), a common skin cancer. These HFSCs cycle between periods of activation, during which they can grow, and quiescence, when they remain dormant.

Using mouse models, White and Lowry applied known cancer-causing genes (oncogenes) to HFSCs and found that during cell quiescence, the cells could not be made to initiate SCC. Once the HFSC were in their active period, they began growing cancer.

We found that this tumor suppression via adult stem cell quiescence was mediated by Pten, a gene important in regulating the cells response to signaling pathways, White said, therefore, stem cell quiescence is a novel form of tumor suppression in hair follicle stem cells, and Pten must be present for the suppression to work.

Understanding cancer suppression through quiescence could better inform preventative strategies in patients susceptible to SCC, such as organ transplant patients, or those taking the drug vemurafenib for melanoma, another type of skin cancer. This study also may reveal parallels between SCC and other cancers in which stem cells have a quiescent phase. This research was supported by the California Institute of Regenerative Medicine (CIRM), University of California Cancer Research Coordinating Committee (CRCC) and National institutes of Health (NIH).

The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLAs Jonsson Comprehensive Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu.

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Adult Stem Cells Found to Suppress Cancer While Dormant

Stem cell warning: experts fear experimental treatments will lead to serious injury

Patients who undergo experimental stem cell treatments run the risk of serious injury, Australian experts have warned.

A team of leading stem cell scientists say the treatments, which involve injecting patients with stem cells from their own fat deposits, have become available to Australian consumers without the protection of regulation or evidence of benefits.

Stem Cells Australia, a consortium of medical and scientific researchers from eight leading Australian universities and research institutes, raised concerns after it became clear the treatments, which are popular overseas, had spread to Australia.

They say vulnerable people with degenerative conditions, such as multiple sclerosis (MS) and Parkinson's disease, are being misled into paying up to $9,000 on stem cell therapies with little or no evidence of the benefits.

However, the industry says there is some good evidence available and treatments are safe as long as patients are only injected with their own unaltered cells.

Practising doctors are forming an industry group to write a code of conduct to keep patients safe.

In a submission to the National Health and Medical Research Council, Stem Cells Australia says many of the practices used by overseas doctors are now being witnessed among Australian practitioners.

These include direct-to-consumer marketing, using patient testimonials instead of evidence, offering the same treatments for unrelated illnesses, lack of safety evidence, no results in peer-reviewed journals, and hefty fees.

Program leader Professor Martin Pera says stem cell treatments are falling through a regulatory loophole because patients are treated with their own cells.

"What's going on is a large scale human experiment without proper scientific procedure and without proper regulatory oversight," he said.

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Stem cell warning: experts fear experimental treatments will lead to serious injury

New treatment eases pet pain

DANIEL TOBIN/ Fairfax NZ

STEMMING PAIN: Lord Claude the st bernard was the first Christchurch dog to receive new stem cell treatment at Total Vets. Kirsten Wylie and Thea Sweeney inject stem cells to ease osteoarthritis in his hips and knees.

Christchurch pet owners have a new way to splash out on their pet care, with the arrival of stem cell treatment costing $2500.

The method uses stem cells from the animal's fat to inject into arthritic joints to relieve pain and limit the need for anti-inflammatories.

Tauranga veterinarian Gil Sinclair started using the technique in his clinic after learning about it in Australia, and has travelled the country helping other clinics set up laboratories.

On Tuesday, Sinclair was in Christchurch to help local clinic Total Vet with its first two patients, a kunekune pig named Samantha and a 78kg st bernard called Lord Claude.

Both animals suffer chronic osteoarthritis, and their respective owners made the leap in the hope of providing pain relief and greater joint use.

Total Vet owner Kirsten Wylie had been keen to get the new treatment in her clinic and approached Lord Claude's owners with the proposal to provide longer-term relief for his arthritis and hip dysplasia.

Stem cells were present throughout all body tissues, but were in particularly high concentration in bone marrow. Using bone marrow was difficult and time-consuming, as extractions had to be cultivated in a laboratory for several weeks to get enough to be useful.

The technique that Sinclair used could be completed in a day. In the morning the animal was brought in and blood and fat samples taken. Only a "heaped tablespoon" of fat was taken, and the stem cells removed and concentrated. Platelets from blood had high levels of naturally occurring stem cell activators, so these were added to the dormant stem cells to "wake" them up.

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New treatment eases pet pain

365 days: 2013 in review

Shutdowns, lethal viruses, typhoons and meteorites much of this years science news seemed to come straight from the set of a Hollywood disaster movie. But there were plenty of feel-good moments, too. Space exploration hit a new high, cash poured in to investigate that most cryptic of human organs, the brain, and huge leaps were made in stem-cell therapies and the treatment of HIV. Here, captured in soundbites, statistics and summaries, is everything you need to know about the science that mattered in 2013.

LUX: Carlos H. Faham

The Large Underground Xenon dark-matter experiment, deep in a mine in South Dakota.

One of the years most important cosmological results was an experimental no-show. The Large Underground Xenon (LUX, pictured) experiment at Sanford Underground Research Facility in Lead, South Dakota 370 kilograms of liquid xenon almost 1.5kilometres down in a gold mine did not see any particles of elusive dark matter flying through Earth. But it put the tightest constraints yet on the mass of dark-matter particles, and their propensity to interact with visible matter. Theoretical physicist Matthew Strassler at Rutgers University in Piscataway, New Jersey, says a consensus is forming that hints of dark matter seen by earlier experiments in the past three years were probably just statistical fluctuations.

PlancK: ESA/Planck Collaboration

Whatever dark matter is, it makes up around 84% of the Universes total matter, according to observations, released in March, of the Universes cosmic microwave background (CMB) by the European Space Agencys Planck satellite. Plancks image (pictured) also strongly supports the hypothesis of inflation, in which the Universe is thought to have expanded rapidly after the Big Bang. A better probe of inflation might be provided through its predicted influence on how the polarization of CMB photons varies across the sky (B-mode polarization). That subtle signal has not been measured yet, but astronomers hopes were raised by news of the first sighting of a related polarization signal, by the South Pole Telescope, in July. And another Antarctic telescope the underground IceCube observatory confirmed this year that the high-energy neutrinos it has detected come from far away in the cosmos, hinting at a new world of neutrino astronomy.

Jae C. Hong/AP

US workers came out in force against the shutdown.

The slow decline of US federal support for research and development spending is already down 16.3% since 2010 reached a new nadir in October, when political brinkmanship led the government to shut down for 16 days. Grant money stopped flowing; work halted at major telescopes, US Antarctic bases and most federal laboratories; and key databases maintained by the government went offline. Many government researchers were declared non-essential and barred by law from visiting their offices and laboratories, or even checking their official e-mail accounts. Since the shutdowns end, grant backlogs and missed deadlines have scrambled agency workloads.

Away from the deadlock in the United States, the European Union negotiated a path to a 201420 research budget of almost 80billion (US$110billion), a 27% rise in real terms over the previous 200713 period. And funding in South Korea, China, Germany and Japan continued to increase (the United Kingdom and France saw little change). But Japans largesse came with the clear understanding that its science investment would bring fast commercial pay-offs. Along similar lines, US Republican politicians are calling for the National Science Foundation to justify every grant it awards as being in the national interest.

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365 days: 2013 in review

Will stem cell therapy help cure spinal cord injury?

Dec. 17, 2013 A systematic survey of the scientific literature shows that stem cell therapy can have a statistically significant impact on animal models of spinal cord injury, and points the way for future studies.

Spinal cord injuries are mostly caused by trauma, often incurred in road traffic or sporting incidents, often with devastating and irreversible consequences, and unfortunately having a relatively high prevalence (250,000 patients in the USA; 80% of cases are male). High-profile campaigners like the late actor Christopher Reeve, himself a victim of sports-related spinal cord injury, have placed high hopes in stem cell transplantation. But how likely is it to work?

This question is addressed in a paper published 17th December in the open access journal PLOS Biology by Ana Antonic, David Howells and colleagues from the Florey Institute and the University of Melbourne, Australia, and Malcolm MacLeod and colleagues from the University of Edinburgh, UK.

Stem cell therapy aims to use special regenerative cells (stem cells) to repopulate areas of damage that result from spinal cord injuries, with the hope of improving the ability to move ("motor outcomes") and to feel ("sensory outcomes") beyond the site of the injury. Many studies have been performed that involve animal models of spinal cord injury (mostly rats and mice), but these are limited in scale by financial, practical and ethical considerations. These limitations hamper each individual study's statistical power to detect the true effects of the stem cell implantation.

This new study gets round this problem by conducting a "meta-analysis" -- a sophisticated and systematic cumulative statistical reappraisal of many previous laboratory experiments. In this case the authors assessed 156 published studies that examined the effects of stem cell treatment for experimental spinal injury in a total of about 6000 animals.

Overall, they found that stem cell treatment results in an average improvement of about 25% over the post-injury performance in both sensory and motor outcomes, though the results can vary widely between animals. For sensory outcomes the degree of improvement tended to increase with the number of cells introduced -- scientists are often reassured by this sort of "dose response," as it suggests a real underlying biologically plausible effect.

The authors went on to use their analysis to explore the effects of bias (whether the experimenters knew which animals were treated and which untreated), the way that the stem cells were cultured, the way that the spinal injury was generated, and the way that outcomes were measured. In each case, important lessons were learned that should help inform and refine the design of future animal studies. The meta-analysis also revealed some surprises that should provoke further investigation -- there was little evidence of any beneficial sensory effects in female animals, for example, and it didn't seem to matter whether immunosuppressive drugs were administered or not.

The authors conclude: "Extensive recent preclinical literature suggests that stem cell-based therapies may offer promise; however the impact of compromised internal validity and publication bias means that efficacy is likely to be somewhat lower than reported here."

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Will stem cell therapy help cure spinal cord injury?