Proper stem cell function requires hydrogen sulfide

Stem cells in bone marrow need to produce hydrogen sulfide in order to properly multiply and form bone tissue, according to a new study from the Center for Craniofacial Molecular Biology at the Ostrow School of Dentistry.

Professor Songtao Shi, principal investigator on the project, said the presence of hydrogen sulfide produced by the cells governs the flow of calcium ions. The essential ions activate a chain of cellular signals that results in osteogenesis, or the creation of new bone tissue, and keeps the breakdown of old bone tissue at a proper level.

Conversely, having a hydrogen sulfide deficiency disrupted bone homeostasis and resulted in a condition similar to osteoporosis -- weakened, brittle bones -- in experimental mice. In humans, osteoporosis can cause serious problems such as bone fractures, mobility limitations and spinal problems; more than 52 million Americans have or are at risk for the disease.

However, Shi and his team demonstrated that the mice's condition could be rescued by administering small molecules that release hydrogen sulfide inside the body. The results indicate that a similar treatment may have potential to help human patients, Shi said.

"These results demonstrate hydrogen sulfide regulates bone marrow mesenchymal stem cells, and restoring hydrogen sulfide levels via non-toxic donors may provide treatments for diseases such as osteoporosis, which can arise from hydrogen sulfide deficiencies," Shi said.

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The above story is based on materials provided by University of Southern California. The original article was written by Beth Newcomb. Note: Materials may be edited for content and length.

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Proper stem cell function requires hydrogen sulfide

First Embryonic Stem Cells Cloned From A Man's Skin

hide captionThis mouse egg (top) is being injected with genetic material from an adult cell to ultimately create an embryo and, eventually, embryonic stem cells. The process has been difficult to do with human cells.

Eighteen years ago, scientists in Scotland took the nuclear DNA from the cell of an adult sheep and put it into another sheep's egg cell that had been emptied of its own nucleus. The resulting egg was implanted in the womb of a third sheep, and the result was Dolly, the first clone of a mammal.

Dolly's birth set off a huge outpouring of ethical concern along with hope that the same techniques, applied to human cells, could be used to treat myriad diseases.

But Dolly's birth also triggered years of frustration. It's proved very difficult to do that same sort of DNA transfer into a human egg.

Last year, scientists in Oregon said they'd finally done it, using DNA taken from infants. Robert Lanza, chief scientific officer at Advanced Cell Technology, says that was an important step, but not ideal for medical purposes.

"There are many diseases, whether it's diabetes, Alzheimer's or Parkinson's disease, that usually increase with age," Lanza says. So ideally scientists would like to be able to extract DNA from the cells of older people not just cells from infants to create therapies for adult diseases.

Lanza's colleagues, including Young Gie Chung at the CHA Stem Cell Institute in Seoul, Korea (with labs in Los Angeles as well), now report success.

Writing in the journal Cell Stem Cell, they say they started with nuclear DNA extracted from the skin cells of a middle-age man and injected it into human eggs donated by four women. As with Dolly, the women's nuclear DNA had been removed from these eggs before the man's DNA was injected. They repeated the process this time starting with the genetic material extracted from the skin cells of a much older man.

hide captionDolly, the first mammal to be genetically cloned from adult cells, poses for the camera in 1997 at the Roslin Institute in Edinburgh, Scotland.

Dolly, the first mammal to be genetically cloned from adult cells, poses for the camera in 1997 at the Roslin Institute in Edinburgh, Scotland.

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First Embryonic Stem Cells Cloned From A Man's Skin

Cloning advance using stem cells from human adult reopens …

Scientists have grown stem cells from adults using cloning techniques for the first time bringing them closer to developing patient-specific lines of cells that can be used to treat a whole host of ailments, from heart disease to blindness.

The research, described in Thursdays online edition of the journal Cell Stem Cell, is a controversial advance likely to reopen the debate over the ethics of human cloning.

The scientists technique was similar to the one used in the first clone of a mammal, Dolly the sheep, which was created in 1996.

They reprogrammed an egg cell by removing its DNA and replaced it with that of an adult donor. Scientists then zapped the cell with electricity, which made it divide and multiply. The resulting cells were identical in DNA to the donor.

The first success in humans was reported last year by scientists at the Oregon Health & Science University and the Oregon National Primate Research Center. But they used donor cells from infants. In this study, the cells came from two men, a 35-year-old and a 75-year-old.

Paul Knoepfler, an associate professor at the University of California at Davis who studies stem cells, called the new research exciting, important, and technically convincing.

In theory you could use those stem cells to produce almost any kind of cell and give it back to a person as a therapy, he said.

In their paper, Young Gie Chung from the Research Institute for Stem Cell Research for CHA Health Systems in Los Angeles, Robert Lanza from Advanced Cell Technology in Marlborough, Mass., and their co-authors emphasized the promise of the technology for new therapies. What they didnt mention but was clear to those working with stem cells was that their work was also an important discovery for human cloning.

While the research published Thursday involves cells that are technically an early stage embryo, the intention is not to try to grow them into a fully formed human. However the techniques in theory could be a first step toward creating a baby with the same genetic makeup as a donor.

Bioethicists call this the dual-use dilemma.

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Cloning advance using stem cells from human adult reopens ...

Top stem cell scientist joins Stemedica

Stem cell scientist Mahendra Rao, former director of the now-defunct Center For Regenerative Medicine at the National Institutes of Health. Photo taken in December, 2013 during a speech by Rao at the World Stem Cell Summit in San Diego.

One of the nation's top stem cell scientists has become an adviser to San Diego's Stemedica, a developer of stem cell-based therapies.

Dr. Mahendra Rao joined Stemedica's scientific and medical advisory board, and will help guide the company's strategy, said Maynard Howe, chief executive of the privately held company. Rao's career as a scientist who has also worked for companies and federal agencies makes him particularly useful, Howe said.

Rao is a medical doctor with a PhD in developmental neurobiology from CalTech. He headed the neurosciences division of the National Institute on Aging. He also led the stem cell division of Carlsbad-based Life Technologies, now a unit of Thermo Fisher Scientific. The two companies are on good terms: Life Technologies sells two kinds of stem cells made by Stemedica, used for research purposes, Howe said.

Rao was most recently founding director of the Center for Regenerative Medicine at the National Institutes of Health, which has been shut down. Rao, who resigned at the end of March, said he was disappointed at the slow pace of funding studies with artificial embryonic stem cells, called induced pluripotent stem cells. Stemedica announced his appointment April 8.

Rao said Wednesday that his goal now is to advance stem cell therapies through the private sector. Stemedica drew his attention because it had developed a method of reliably generating "clinically compliant" stem cells suitable for use in therapy.

In addition, Rao said he likes that Stemedica is developing combination stem cell therapies, using a variety called mesenchymal stem cells. This variety of stem cell generates chemicals that promote short-term regrowth and seems to enhance the survival of other transplanted stem cells. For example, mesenchymal stem cells could help transplanted neural stem cells integrate into the brain.

"That's a high-risk process and it's a much more difficult road, but they seem to be willing to do that," Rao said.

He has also rejoined the board of Q Therapeutics, a Salt Lake City company developing treatments for spinal cord injuries and other neurological disorders. Rao is the company's scientific founder, but had to leave the company when he joined the NIH.

Stemedica and its affiliated companies are undertaking multiple clinical trials of stem cell therapies. One of the most advanced is for stroke, Howe said. See utsandiego.com/stemedicastroke1 for detailed information.

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Top stem cell scientist joins Stemedica

Stem Cell therapy on animals may be medicine of the future

Two Central Pennsylvania dogs are receiving a regenerative therapy for arthritis thats unprecedented for this area and less expensive than standard surgery. Stem Cell therapy is a way to repair damaged tissue and treat injury. When dealing with dogs, veterinarians say its the future of treatments and its becoming less costly.

Gunny is a 7-year-old German Shepard. He underwent the revolutionary stem cell therapy at the Palmyra Animal Clinic. Vets say the stem cell therapy is a way to combat Gunnys arthritis in his hips. Doctors collected fatty tissue from his shoulder, processed the stem cells in the lab and injected the cells back into his hips. This happens all in one day for around $1500. Prior to this, surgery could cost around $3,000.

Dr. Calvin Clements of the Palmyra Animal Clinic says, Injected in a damaged joint or ligament, these cells will take on that characteristic and differentiate into the cartilage or tissue were dealing with and help to regenerate it.

Dr. Clements says results are noticeable in about a month. On average, animals improve 85%.

For more information, contact the Palmyra Animal Clinic at 717-838-5451.

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Stem Cell therapy on animals may be medicine of the future

Stem-Cell Treatment for Blindness Moving Through Patient Testing

Advanced Cell Technology is testing a stem-cell treatment for blindness that could preserve vision and potentially reverse vision loss.

Vision support: The cells used in Advanced Cell Technologys clinical trials produce dark pigments and cobblestone-like patterns that can be readily recognized in cultures.

A new treatment for macular degeneration is close to the next stage of human testinga noteworthy event not just for the millions of patients it could help, but for its potential to become the first therapy based on embryonic stem cells.

This year, the Boston-area company Advanced Cell Technology plans to move its stem-cell treatment for two forms of vision loss into advanced human trials. The company has already reported that the treatment is safe (see Eye Study Is a Small but Crucial Advance for Stem-Cell Therapy), although a full report of the results from the early, safety-focused testing has yet to be published. The planned trials will test whether it is effective. The treatment will be tested both on patients with Stargardts disease (an inherited form of progressive vision loss that can affect children) and on those with age-related macular degeneration, the leading cause of vision loss among people 65 and older.

The treatment is based on retinal pigment epithelium (RPE) cells that have been grown from embryonic stem cells. A surgeon injects 150 microliters of RPE cellsroughly the amount of liquid in three raindropsunder a patients retina, which is temporarily detached for the procedure. RPE cells support the retinas photoreceptors, which are the cells that detect incoming light and pass the information on to the brain.

Although complete data from the trials of ACTs treatments have yet to be published, the company has reported impressive results with one patient, who recovered vision after being deemed legally blind. Now the company plans to publish the data from two clinical trials taking place in the U.S. and the E.U. in a peer-reviewed academic journal. Each of these early-stage trials includes 12 patients affected by either macular degeneration or Stargardts disease.

The more advanced trials will have dozens of participants, says ACTs head of clinical development, Eddy Anglade. If proved safe and effective, the cellular therapy could preserve the vision of millions affected by age-related macular degeneration. By 2020, as the population ages, nearly 200 million people worldwide will have the disease, estimate researchers. Currently, there are no treatments available for the most common form, dry age-related macular degeneration.

ACTs experimental treatment has its origins in a chance discovery that Irina Klimanskaya, the companys director of stem-cell biology, made while working with embryonic stem cells at Harvard University. These cells have the power to develop into any cell type, and in culture they often change on their own. A neuron here, a fat cell thereindividual cells in a dish tend to take random walks down various developmental paths. By supplying the cultures with fresh nutrients but otherwise leaving them to their own devices for several weeks, Klimanskaya discovered that the stem cells often developed into darkly pigmented cells that grew in a cobblestone-like pattern. She suspected that they were developing into RPE cells, and molecular tests backed her up.

Now that her discovery has advanced into an experimental treatment, Klimanskaya says she is excited by the hints that it may be able to preserve, and perhaps restore, sight. She recalls a voice mail she received during her second year at ACT: a person blinded by an inherited condition thanked her for her work, whether or not there was a treatment available for him. When you get a message like this, you feel like you are not doing it in vain, she says.

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Stem-Cell Treatment for Blindness Moving Through Patient Testing

Pioneers in Regenerative Therapy to Discuss New Trends in Stem Cell Medicine

Washington (PRWEB) April 15, 2014

Research that resulted in the first stem cells that are pluripotentthose that have the potential to differentiate into almost any cell in the bodywill be the backdrop for a discussion about trends in regulation in the field of regenerative medicine at the DIA 2014 50th Annual Meeting, June 15 to 19 in San Diego.

Chaired by Shinji Miyake, professor of clinical research for the Keio University School of Medicine in Japan, the session Pioneering Regenerative Medicine: Trends in Regulations for New Therapy will introduce the worlds first clinical research of induced pluripotent stem (iPS) cell products, conducted in Japan, and review updated regulatory guidance to bring regenerative medicine to patients who need healthy tissue or organs. The session will be held June 16 at 8:30 a.m. in the San Diego Convention Center.

iPS cells are stem cells that can be generated directly from adult cells. These cells can multiply indefinitely and represent a single source of cells, such as heart, neural, pancreatic and liver, that can be used to replace damaged cells.

In 2006, Japanese physician and researcher Shinya Yamanaka led a team to generate iPS cells from adult mouse tissue using gene therapy. This work led to a Nobel Prize in Physiology or Medicine in 2012 for the discovery that mature cells can be reprogrammed to become pluripotent.

We are honored to host pioneers of this unique field of medicine at the DIA Annual Meeting to share their experiences in the planning of the first clinical research of iPS cell productswhich have the ability to enhance research worldwide, said Barbara L. Kunz, DIA global chief executive. Their expert knowledge of issues and solutions in the application of the regenerative therapies will benefit all who advocate for and drive innovative medicine.

The session will also feature a presentation about the application of iPS cells to retinal diseases by Masayo Takahashi, project leader for the RIKEN Center for Developmental Biology in Japan, along with a European Medicines Agency (EMA) presentation by Dariusz Sladowski, researcher and member of the Committee for Advanced Therapies at EMA.

ABOUT DIA: DIA is the global connector in the life sciences product development process. Our association of more than 18,000 members builds productive relationships by bringing together regulators, innovators and influencers to exchange knowledge and collaborate in an impartial setting. DIAs network creates unparalleled opportunities for the exchange of knowledge and has the interdisciplinary experience to prepare for future developments. DIA is an independent, nonprofit organization with its global center in Washington, D.C., USA; regional offices covering North and South America (Horsham, Pa., USA); Europe, North Africa and the Middle East (Basel, Switzerland); and Japan (Tokyo), India (Mumbai) and China (Beijing). For more information, visit http://www.diahome.org.

ABOUT DIAs 2014 50th ANNUAL MEETING: Celebrate the Past Invent the Future is the largest multidisciplinary event that brings together a community of life sciences professionals at all levels and across all disciplines involved in the discovery, development and life cycle management of medical products. The meeting aims to foster innovation that will lead to the development of safe and effective medical products and therapies for patients. For more information, visit http://www.diahome.org/dia2014.

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Pioneers in Regenerative Therapy to Discuss New Trends in Stem Cell Medicine

MGH Findings Suggest Novel Treatment Approach For Brain Tumors

By Estel Grace Masangkay

A team of investigators from the Massachusetts General Hospital (MGH) has identified four transcription factors characterizing the small proportion of glioblastoma cells behind the aggressiveness and treatment resistance of the brain tumor. The teams findings suggest a novel approach to treating glioblastoma stem cells.

The researchers identified a combination of four transcription factors (POU3F2, SOX2, SALL2 and OLIG2) able to reprogram differentiated tumor cells back into glioblastoma stem cells in vitro as well as in an animal model. The team confirmed that the four factors and their corresponding regulatory elements were active in from 2 to 7 percent of human glioblastoma cells, which also expressed a known stem cell marker.

Dr. Mario Suv of the MGH Department of Pathology and Center for Cancer Research, and co-lead author, said, We have identified a code of molecular switches that control a very aggressive subpopulation of brain cancer cells, so-called glioblastoma stem cells. Understanding what drives these aggressive cells will give us insights into alternative ways of eliminating them and potentially changing the course of this very deadly tumor.

Findings show that inhibition of a crucial regulatory protein complexs action involving a known target gene of one of the core transcription factors caused glioblastoma stem cells to lose their stem-like properties and eventually die.

Dr. Bradley Bernstein of the MGH Pathology and the MGH Cancer Center, and senior author of the study, said, This study brings us back to the fundamental idea that there are many reasons that cancer cells can be aggressive. Just as normal cells with the same genome differentiate into many different cell types, a single tumor characterized by specific genetic mutations can contain many different types of cells stem-like and more differentiated cells with the difference being rooted in their epigenetic information. Identifying the drivers of these different cellular states in glioblastoma stem cells could offer us the best opportunity for treating what remains an extremely difficult-to -treat tumor.

The MGH teams findings will be published in the April 24 issue of Cell and will receive an advance online release.

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MGH Findings Suggest Novel Treatment Approach For Brain Tumors