Category Archives: Stem Cells

ScienceDaily (June 28, 2012) Johns Hopkins researchers, working with an international consortium, say they have generated stem cells from skin cells from a person with a severe, early-onset form of Huntington's disease (HD), and turned them into neurons that degenerate just like those affected by the fatal inherited disorder.

By creating "HD in a dish," the researchers say they have taken a major step forward in efforts to better understand what disables and kills the cells in people with HD, and to test the effects of potential drug therapies on cells that are otherwise locked deep in the brain.

Although the autosomal dominant gene mutation responsible for HD was identified in 1993, there is no cure. No treatments are available even to slow its progression.

The research, published in the journal Cell Stem Cell, is the work of a Huntington's Disease iPSC Consortium, including scientists from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, as well as six other groups. The consortium studied several other HD cell lines and control cell lines in order to make sure results were consistent and reproducible in different labs.

The general midlife onset and progressive brain damage of HD are especially cruel, slowly causing jerky, twitch-like movements, lack of muscle control, psychiatric disorders and dementia, and -- eventually -- death. In some cases (as in the patient who donated the material for the cells made at Johns Hopkins), the disease can strike earlier, even in childhood.

"Having these cells will allow us to screen for therapeutics in a way we haven't been able to before in Huntington's disease," saysChristopher A. Ross, M.D., Ph.D., a professor of psychiatry and behavioral sciences, neurology, pharmacology and neuroscience at the Johns Hopkins University School of Medicine and one of the study's lead researchers. "For the first time, we will be able to study how drugs work on human HD neurons and hopefully take those findings directly to the clinic."

Ross and his team, as well as other collaborators at Johns Hopkins and Emory University, are already testing small molecules for the ability to block HD iPSC degeneration.These small molecules have the potential to be developed into novel drugs for HD.

The ability to generate from stem cells the same neurons found in Huntington's disease may also have implications for similar research in other neurodegenerative diseases such as Alzheimer's and Parkinson's.

To conduct their experiment, Ross took a skin biopsy from a patient with very early onset HD.When seen by Ross at the HD Center at Hopkins, the patient was just seven years old. She had a very severe form of the disease, which rarely appears in childhood, and of the mutation that causes it. Using cells from a patient with a more rapidly progressing form of the disease gave Ross' team the best tools with which to replicate HD in a way that is applicable to patients with all forms of HD.

Her skin cells were grown in culture and then reprogrammed by the lab of Hongjun Song, Ph.D., a professor at Johns Hopkins' Institute for Cell Engineering, into induced pluripotent stem cells. A second cell line was generated in an identical fashion in Dr. Ross's lab from someone without HD. Simultaneously, other HD and control iPS cell lines were generated as part of the NINDS funded HD iPS cell consortium.

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Turning skin cells into brain cells: Huntington's disease in a dish

Neuralstem, the Rockville company thats developing a stem cell treatment for patients with amyotrophic lateral sclerosis, has begun testing the safety of its treatment for major depressive disorder.

The compound, NSI-189, stimulates new neuron growth in the brain's hippocampus region, which scientists think is involved in depression and other conditions, including Alzheimer's disease, anxiety and post-traumatic stress disorder, according to a company statement. The phase 1b study involves 24 depressed patients and is expected to run six months.

"We believe it could help patients who suffer from depression via a new mechanism that does not seek to modulate brain chemistry, but rather stimulates new neuron growth in the hippocampus and increases hippocampal volume, thereby potentially addressing the problem at the source," Karl Johe, Neuralstem's chief scientific officer, said in the statement.

The company has researched hippocampal stem cell lines since 2000 and in 2009 won U.S. patents for four chemical entities that generate new neurons. In studies, NSI-189 stimulated such growth in mice.

In other Maryland bioscience industry news:

Supernus Pharmaceuticals has received tentative marketing approval from the Food and Drug Administration for its once-daily, extended release version of an epilepsy treatment.

The FDA said it has completed its review of Trokendi XR and no more clinical trials are required. Final approval hinges on resolving a marketing exclusivity issue that involves a specific pediatric population, according to the FDA's letter to Supernus.

Trokendi XR is an extended-release version of topimarate, which is marketed as Topamax by Janssen Pharmaceuticals of Titusville, N.J., to treat seizures and migraine headaches.

"We will continue to work closely with the FDA to further understand the outstanding issue and move forward towards final approval," CEO Jack Khattar said in the statement.

Supernus, which went public this year, also said the FDA denied a petition filed in 2011 by Upsher Smith Laboratories related to its Trokendi XR application.

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Gazette.Net: Rockville biotech tests stem cells for depression

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/4ghhzd/handbook_of_stem_c) has announced the addition of Elsevier Science and Technology's new report "Handbook of Stem Cells, Two-Volume Set. Edition No. 2" to their offering.

New discoveries in the field of stem cells increasingly dominate the news and scientific literature revealing an avalanche of new knowledge and research tools that are producing therapies for cancer, heart disease, diabetes, and a wide variety of other diseases that afflict humanity. The Handbook of Stem Cells integrates this exciting area of life science, combining in two volumes the requisites for a general understanding of adult and embryonic stem cells. Organized in two volumes entitled Pluripotent Stem Cells & Cell Biology and Adult & Fetal Stem Cells, this work contains contributions from the world's experts in stem cell research to provide a description of the tools, methods, and experimental protocols needed to study and characterize stem cells and progenitor populations as well as a the latest information of what is known about each specific organ system.

- Provides comprehensive coverage on this highly topical subject

- Contains contributions by the foremost authorities and premiere names in the field of stem cell research

- Companion website contains over 250 color figures in presentation format

For more information visit http://www.researchandmarkets.com/research/4ghhzd/handbook_of_stem_c

Source: Elsevier Science and Technology

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Research and Markets: Handbook of Stem Cells, Two-Volume Set. Edition No. 2

Public release date: 28-Jun-2012 [ | E-mail | Share ]

Contact: Stephanie Desmon sdesmon1@jhmi.edu 410-955-8665 Johns Hopkins Medical Institutions

Johns Hopkins researchers, working with an international consortium, say they have generated stem cells from skin cells from a person with a severe, early-onset form of Huntington's disease (HD), and turned them into neurons that degenerate just like those affected by the fatal inherited disorder.

By creating "HD in a dish," the researchers say they have taken a major step forward in efforts to better understand what disables and kills the cells in people with HD, and to test the effects of potential drug therapies on cells that are otherwise locked deep in the brain.

Although the autosomal dominant gene mutation responsible for HD was identified in 1993, there is no cure. No treatments are available even to slow its progression.

The research, published in the journal Cell Stem Cell, is the work of a Huntington's Disease iPSC Consortium, including scientists from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, as well as six other groups. The consortium studied several other HD cell lines and control cell lines in order to make sure results were consistent and reproducible in different labs.

The general midlife onset and progressive brain damage of HD are especially cruel, slowly causing jerky, twitch-like movements, lack of muscle control, psychiatric disorders and dementia, and eventually death. In some cases (as in the patient who donated the material for the cells made at Johns Hopkins), the disease can strike earlier, even in childhood.

"Having these cells will allow us to screen for therapeutics in a way we haven't been able to before in Huntington's disease," says Christopher A. Ross, M.D., Ph.D., a professor of psychiatry and behavioral sciences, neurology, pharmacology and neuroscience at the Johns Hopkins University School of Medicine and one of the study's lead researchers. "For the first time, we will be able to study how drugs work on human HD neurons and hopefully take those findings directly to the clinic."

Ross and his team, as well as other collaborators at Johns Hopkins and Emory University, are already testing small molecules for the ability to block HD iPSC degeneration. These small molecules have the potential to be developed into novel drugs for HD.

The ability to generate from stem cells the same neurons found in Huntington's disease may also have implications for similar research in other neurodegenerative diseases such as Alzheimer's and Parkinson's.

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Turning skin cells into brain cells

Public release date: 28-Jun-2012 [ | E-mail | Share ]

Contact: Dr. Stefan Wiese stefan.wiese@rub.de 49-234-322-2041 Ruhr-University Bochum

RUB biologists have deliberately transformed stem cells from the spinal cord of mice into immature nerve cells. This was achieved by changing the cellular environment, known as the extracellular matrix, using the substance sodium chlorate. Via sugar side chains, the extracellular matrix determines which cell type a stem cell can generate. "Influencing precursor cells pharmacologically so that they transform into a particular type of cell can help in cell replacement therapies in future" says Prof. Dr. Stefan Wiese, head of the Molecular Cell Biology work group. "Therapies, for example, for Parkinson's, multiple sclerosis or amyotrophic lateral sclerosis could then become more efficient." The team describes its findings in Neural Development.

Sulphate determines the fate of stem cells

Sodium chlorate acts on metabolism enzymes in the cell which attach sulphate groups to proteins. If these sulphates are not installed, the cell continues to form proteins for the extracellular matrix, but with modified sugar side chains. These chains in turn send out signals that define the fate of the stem cells. Stem cells can not only develop into nerve cells, but also form astrocytes or oligodendrocytes, which are, for instance, responsible for the mineral balance of the nerve cells or which form their insulation layer. What happens to the stem cells if the sulphate pattern is changed by sodium chlorate was examined by Dr. Michael Karus and his colleagues.

Positive side effects: nerve cells remain immature

The RUB-laboratories of Prof. Dr. Stefan Wiese, Prof. Dr. Andreas Faissner and Prof. Dr. Irmgard Dietzel-Meyer collaborated for the study. Using antibodies, the researchers showed that cells which they had treated with sodium chlorate developed into nerve cells. They also analysed the flow of sodium ions into the cells. The result: treated cells showed a lower sodium current than mature nerve cells. Sodium chlorate thus favours the development of stem cells into nerve cells, but, at the same time, also inhibits the maturation - a positive side effect, as Wiese explains: "If sodium chlorate stops the nerve cells in an early developmental phase, this could enable them to integrate into the nervous system following a transplant better than mature nerve cells would do."

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Bibliographic record

M. Karus, S. Samtleben, C. Busse, T. Tsai, I.D. Dietzel, A. Faissner, S. Wiese (2012): Normal sulphation levels regulate spinal cord neural precursor cell proliferation and differentiation, Neural Development, doi: 10.1186/1749-8104-7-20

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Taking the fate of stem cells in hand: RUB researchers generate immature nerve cells

Washington, June 28 : In a new study, researchers have successfully reversed diabetes in mice using stem cells, thereby paving the way for a breakthrough treatment for a disease that affects millions worldwide.

The research by Timothy Kieffer, from University of British Columbia in collaboration with scientists from the New Jersey-based BetaLogics, is the first to show that human stem cell transplants can successfully restore insulin production and reverse diabetes in mice.

Crucially, they re-created the "feedback loop" that enables insulin levels to automatically rise or fall based on blood glucose levels.

After the stem cell transplant, the diabetic mice were weaned off insulin, a procedure designed to mimic human clinical conditions.

Three to four months later, the mice were able to maintain healthy blood sugar levels even when being fed large quantities of sugar.

Transplanted cells removed from the mice after several months had all the markings of normal insulin-producing pancreatic cells.

"We are very excited by these findings, but additional research is needed before this approach can be tested clinically in humans," Kieffer said.

"The studies were performed in diabetic mice that lacked a properly functioning immune system that would otherwise have rejected the cells. We now need to identify a suitable way of protecting the cells from immune attack so that the transplant can ultimately be performed in the absence of any immunosuppression," Kieffer added.

The study has been recently published online in Diabetes. (ANI)

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Stem cells may help reverse diabetes

Public release date: 28-Jun-2012 [ | E-mail | Share ]

Contact: Nicole White nicole.white@cshs.org 310-423-5215 Cedars-Sinai Medical Center

LOS ANGELES (EMBARGOED UNTIL NOON EDT ON JUNE 28, 2012) Cedars-Sinai scientists have joined with expert colleagues around the globe in using stem cells to develop a laboratory model for Huntington's disease, allowing researchers for the first time to test directly on human cells potential treatments for this fatal, inherited disorder.

As explained in a paper published June 28 on the Cell Stem Cell website and scheduled for print in the journal's Aug. 3 issue, scientists at Cedars-Sinai's Regenerative Medicine Institute and the University of Wisconsin took skin cells from patients with Huntington's disease and reprogrammed them into powerful stem cells; these were then made into the nervous system cells affected by the disease. Seven laboratories around the world collaborated to demonstrate the cells had hallmarks of Huntington's.

"This Huntington's 'disease in a dish' will enable us for the first time to test therapies on human Huntington's disease neurons," said Clive Svendsen, PhD, director of the Cedars-Sinai Regenerative Medicine Institute and a senior author of the study. "In addition to increasing our understanding of this disorder and offering a new pathway to identifying treatments, this study is remarkable because of the extensive interactions between a large group of scientists focused on developing this model. It's a new way of doing trailblazing science."

The Huntington's Disease iPSC Consortium united some of the world's top scientists working on this disease. Cedars-Sinai researchers took skin cells from a several Huntington's patients, including a six-year-old with a severe juvenile form of the disease. They genetically reprogrammed these tissues into induced pluripotent stem cells, which can be made into any type of cell in the body. The cells lines were banked by scientists at Cedars-Sinai and scrutinized by all consortium members for differences that may have led to the disease. These cell lines are now an important resource for Huntington's researchers and have been made available via a National Institutes of Health-funded repository at Coriell Institute for Medical Research in New Jersey.

Huntington's, known to the public, for example, as the cause of folksinger Woody Guthrie's death, typically strikes patients in midlife. It causes jerky, twitching motions, loss of muscle control, psychiatric disorders and dementia; the disease ultimately is fatal. In rare, severe cases, the disorder appears in childhood.

Researchers believe that Huntington's results from a mutation in the huntintin gene, leading to production of an abnormal protein and ultimately cell death in specific areas of the brain that control movement and cognition. There is no cure for Huntington's, nor therapies to slow its progression.

The consortium showed Huntington's cell deficits or how they differ from normal cells, including that they were less likely to survive cultivation in the petri dish. Scientists tried depriving them of a growth factor present around normal cells, or "stressing" them, and found that Huntington's neurons died even faster.

"It was great that these characteristics were seen not only in our laboratory, but by all of the consortium members using different techniques," said Virginia Mattis, a post-doctoral scientist at the Cedars-Sinai Regenerative Medicine Institute and one of the lead authors of the study. "It was very reassuring and significantly strengthens the value of this study."

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Cedars-Sinai researchers, with stem cells and global colleagues, develop Huntingtons research tool

HOUSTON -

Pandu, the 286-pound Malayan tiger stretched out on the gurney in the Houston Zoo's hospital, had bone chips big ones in his right elbow.

Ivy the leopard, being prepped in another room, also needed medical treatment for her limp. The zoo's 68-pound black cat, which had arthroscopic surgery in 2009, was showing signs of pain again in her elbows.

The zoo staff was worried.

"I imagine we are going to end up euthanizing her at some point if it can't be fixed," said Beth Schaefer, the zoo's curator of carnivores and primates.

With two big cats needing attention, surgeon Brian Beale of Gulf Coast Veterinary Specialists and stem-cell specialists at InGeneron Inc. donated their services to treat the animals. While Beale removed bone chips and cleaned the joints during arthroscopic surgery, InGeneron staffers produced stem cells from each animal's body fat.

When the surgeries were complete, Beale injected the stem cells, which had taken about two hours to process for each big cat, into the animals' joints to promote faster healing.

Pandu, always a big baby looking for attention, was moving a bit slowly the day after surgery.

Feisty Ivy pretended nothing was wrong.

A week after the surgery, Houston Zoo veterinarian Lauren Howard says neither animal has suffered complications. Pandu, with mild swelling, was released into his exhibit half-days on Monday.

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Stem cells help some ailing Houston Zoo creatures

Editor's Choice Main Category: Pancreatic Cancer Also Included In: Cancer / Oncology;Stem Cell Research Article Date: 27 Jun 2012 - 10:00 PDT

Current ratings for: Metformin Shows Promise For Pancreatic Cancer Patients

3.67 (3 votes)

In combination with the standard chemotherapy for pancreatic cancer, metformin was observed to efficiently eradicate both cancer stem cells and more differentiated cancer cells that form the bulk of the tumor. The study was presented at the American Association for Cancer Research's Pancreatic Cancer: Progress and Challenges conference in Lake Tahoe, Nev., from June 18-21, 2012 by Christopher Heeschen, M.D., Ph.D., a professor for experimental medicine at the Spanish National Cancer Research Centre in Madrid.

Heeschen said that the majority of clinical trials of pancreatic cancer during the last 15 years failed to demonstrate a notable improvement in the average survival, which indicates for various reasons the methods used in these trials were insufficient. However, within the last few years, scientists have discovered cancer stem cells, which contrary to the cancer cells that make up the bulk of the tumor, consist of a small subset of cells that are resistant to conventional therapy.

He continued:

The team discovered that metformin-pretreated cancer stem cells proved especially sensitive to changes to their metabolism through the activation of AMPK, as metformin killed the cancer stem cells, but only stopped the cell's growth in more differentiated cancer cells.

Heeschen explained:

Their findings were supported in an experiment with mice, in which they treated immunocompromised mice that were implanted with various sets of patient-derived tumors with a combination of metformin and the standard chemotherapeutic treatment for pancreatic cancer, gemcitabine. The results were reduced tumors and a prevention of relapse in contrast to mice treated only with metformin or with gemcitabine.

Heeschen remarked: "Intriguingly, in all tumors treated with metformin to date, relapse of disease was efficiently prevented and there were no noticeable adverse effects."

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Metformin Shows Promise For Pancreatic Cancer Patients

VANCOUVER In a world's first, University of B.C. scientists have used human embryonic stem cell transplants to reverse diabetes in mice.

A 13-member team, whose work was published Wednesday in the journal Diabetes, showed that as the stem cells matured into insulin-secreting cells (beta-cells in the pancreas), a few dozen diabetic mice were weaned gradually off insulin over a period of months.

The study, which cost at least $500,000, was funded by the Canadian Institutes of Health Research, the Stem Cell Network of Canada, Stem Cell Technologies of Vancouver, the Juvenile Diabetes Research Foundation and the Michael Smith Foundation of Health Research. About half the research team was comprised of scientists from the New Jersey private research and development arm (BetaLogics Venture) of Janssen Pharmaceuticals.

"It took about four to five months for the (stem) cells to become functional in our experiments and the mice were able to maintain good blood glucose levels even when fed a high-glucose diet," said lead author Timothy Kieffer, a UBC professor in the department of cellular and physiological sciences.

Type 1 otherwise known as juvenile diabetes is an autoimmune disease in which a patient's immune system kills off insulin-producing cells in the pancreas. Typically, patients must inject themselves with insulin or use insulin pumps to control their blood glucose levels.

While pancreatic islet cell transplantation pioneered at the University of Alberta several years ago has been shown to be an effective way of reducing dependence on insulin injections, such treatments are costly and cumbersome since they require cells culled from dead bodies; such cells are always in short supply. As well, islet cell transplant patients must forever take anti-rejection drugs that can cause organ damage.

Although the research showed that stem cells have great potential as a diabetes cure, it also revealed there are still a few pitfalls to overcome before agencies like the Food and Drug Administration in the United States or Health Canada approve such a therapy. Some mice developed bone or cartilage growths in areas where the cells were inserted, an unacceptable side-effect that future experiments must resolve.

Another obstacle is that the mice used in the study weren't typical; they were a special strain, bred to be immuno-compromised so they wouldn't reject the human cells as foreign invaders. Studies are continuing at UBC, in many more mice, to determine the feasibility of encapsulating stem cells in a membrane material that won't be recognized as a foreign body and rejected.

Kieffer said he's extremely encouraged by the fact that the mice not only were weaned off their need for insulin but also lived well and long, even though they were bred to be immune-deficient. Still, he said, researchers must find ways to fine-tune the approach so that cells don't evolve into something other than what's desired.

In the early stages of the experiment, some mice developed fluid-filled cysts, a problem that was rectified in the laboratory with a cell culture medium change.

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Canadian scientists use stem cells to reverse diabetes in mice