UCLA study finds link between neural stem cell overgrowth and autism-like behavior in mice

PUBLIC RELEASE DATE:

9-Oct-2014

Contact: Mark Wheeler mwheeler@mednet.ucla.edu 310-794-2265 University of California - Los Angeles @uclanewsroom

People with autism spectrum disorder often experience a period of accelerated brain growth after birth. No one knows why, or whether the change is linked to any specific behavioral changes.

A new study by UCLA researchers demonstrates how, in pregnant mice, inflammation, a first line defense of the immune system, can trigger an excessive division of neural stem cells that can cause "overgrowth" in the offspring's brain.

The paper appears Oct. 9 in the online edition of the journal Stem Cell Reports.

"We have now shown that one way maternal inflammation could result in larger brains and, ultimately, autistic behavior, is through the activation of the neural stem cells that reside in the brain of all developing and adult mammals," said Dr. Harley Kornblum, the paper's senior author and a director of the Neural Stem Cell Research Center at UCLA's Semel Institute for Neuroscience and Human Behavior.

In the study, the researchers mimicked environmental factors that could activate the immune system such as an infection or an autoimmune disorder by injecting a pregnant mouse with a very low dose of lipopolysaccharide, a toxin found in E. coli bacteria. The researchers discovered the toxin caused an excessive production of neural stem cells and enlarged the offspring's' brains.

Neural stem cells become the major types of cells in the brain, including the neurons that process and transmit information and the glial cells that support and protect them.

Notably, the researchers found that mice with enlarged brains also displayed behaviors like those associated with autism in humans. For example, they were less likely to vocalize when they were separated from their mother as pups, were less likely to show interest in interacting with other mice, showed increased levels of anxiety and were more likely to engage in repetitive behaviors like excessive grooming.

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UCLA study finds link between neural stem cell overgrowth and autism-like behavior in mice

UCSF, UC Berkeley scientists join forces in new Glenn Center for Aging Research

PUBLIC RELEASE DATE:

8-Oct-2014

Contact: Pete Farley peter.farley@ucsf.edu 415-502-6397 University of California - San Francisco @ucsf

Researchers at UC San Francisco and UC Berkeley have teamed up to create an innovative, integrated center for research on neurodegenerative diseases. Supported by a $3 million grant from the Glenn Foundation for Medical Research, the new center aims to pave the way to developing novel treatments for diseases such as Alzheimer's disease and Parkinson's disease by investigating the many ways that proteins can malfunction within cells.

In particular, the center's work will focus on a type of protein called the prion, which displays characteristics of infectious agents and is responsible for "mad cow" disease and a related, devastating human brain disorder known as Creutzfeldt-Jakob disease (CJD).

Stanley B. Prusiner, MD, UCSF professor of neurology, and Andrew Dillin, PhD, the Thomas and Stacey Siebel Distinguished Chair of Stem Cell Research at UCB and a Howard Hughes Medical Institute investigator, will codirect the new inter-campus program, known as the Paul F. Glenn Center for Aging Research. Ten additional researchers from UCSF and 13 from UCB will contribute to the center's work, with more recruitments to come.

"The Glenn Foundation is pleased to welcome UCSF and UC Berkeley to the Glenn Consortium for Research in Aging," said Mark R. Collins, president of the Glenn Foundation for Medical Research, which is based in Santa Barbara, Calif. "I had the pleasure to work with Dr. Dillin previously, when he led the Glenn Center for Aging Research at the Salk Institute for Biological Sciences prior to moving to UC Berkeley. I've known Dr. Prusiner and followed his work for many years and it is a propitious time for us to assist these two leaders in biological research to discover treatments for age-related neurodegenerative disease."

In 1997, Prusiner, director of UCSF's Institute for Neurodegenerative Diseases, received the Nobel Prize in Physiology or Medicine for his discovery of prions, which he demonstrated were an abnormally folded form of normal proteins that set up a template for replication in the brain. According to Prusiner, recent work provides persuasive evidence that, in addition to mad cow disease and CJD, many common neurodegenerative diseases, including Alzheimer's and Parkinson's, are caused by abnormally folded forms of normal proteins functioning as prions.

Dillin agrees that prions are ideal targets for research and novel therapeutic approaches. "The Glenn Foundation's confidence to support our hypothesis is greatly appreciated," he said, adding that the combination of UCSF's medical mission with the strong basic research traditions of both campuses will make the new Glenn Center's work uniquely powerful.

Proteins are crucial for many of a cell's normal functions, but as people age, cells' quality-control mechanisms become less efficient. Normally these systems ensure that proteins are properly formed, and target badly formed or "worn-out" proteins for destruction. But as the effectiveness of cellular quality control wanes over time, improperly formed proteins, including prions, can begin to accumulate.

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UCSF, UC Berkeley scientists join forces in new Glenn Center for Aging Research

Study Finds Link Between Neural Stem Cell Overgrowth and Autism-Like Behavior in Mice

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Newswise People with autism spectrum disorder often experience a period of accelerated brain growth after birth. No one knows why, or whether the change is linked to any specific behavioral changes.

A new study by UCLA researchers demonstrates how, in pregnant mice, inflammation, a first line defense of the immune system, can trigger an excessive division of neural stem cells that can cause overgrowth in the offsprings brain.

The paper appears Oct. 9 in the online edition of the journal Stem Cell Reports.

We have now shown that one way maternal inflammation could result in larger brains and, ultimately, autistic behavior, is through the activation of the neural stem cells that reside in the brain of all developing and adult mammals, said Dr. Harley Kornblum, the papers senior author and a director of the Neural Stem Cell Research Center at UCLAs Semel Institute for Neuroscience and Human Behavior.

In the study, the researchers mimicked environmental factors that could activate the immune system such as an infection or an autoimmune disorder by injecting a pregnant mouse with a very low dose of lipopolysaccharide, a toxin found in E. coli bacteria. The researchers discovered the toxin caused an excessive production of neural stem cells and enlarged the offsprings brains.

Neural stem cells become the major types of cells in the brain, including the neurons that process and transmit information and the glial cells that support and protect them.

Notably, the researchers found that mice with enlarged brains also displayed behaviors like those associated with autism in humans. For example, they were less likely to vocalize when they were separated from their mother as pups, were less likely to show interest in interacting with other mice, showed increased levels of anxiety and were more likely to engage in repetitive behaviors like excessive grooming.

Kornblum, who also is a professor of psychiatry, pharmacology and pediatrics at the David Geffen School of Medicine at UCLA, said there are many environmental factors that can activate a pregnant womans immune system.

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Study Finds Link Between Neural Stem Cell Overgrowth and Autism-Like Behavior in Mice

Cure for Type 1 diabetes imminent after Harvard stem-cell breakthrough

We are now just one pre-clinical step away from the finish line, said Prof Melton.

Asked about his childrens reaction he said: "I think like all kids, they always assumed that if I said I'd do this, I'd do it,

"It was gratifying to know that we can do something that we always thought was possible.

The stem cell-derived beta cells are presently undergoing trials in animal models, including non-human primates, where they are still producing insulin after several months, Prof Melton said.

Type 1 diabetes is an autoimmune condition that causes the pancreas to stop producing insulin - the hormone that regulates blood glucose levels.

If the amount of glucose in the blood is too high it can seriously damage the body's organs over time.

While diabetics can keep their glucose levels under general control by injecting insulin, that does not provide the fine tuning necessary to properly control metabolism, which can lead to devastating complications such as blindness or loss of limbs.

Around 10 per cent of all diabetes is Type 1, but it is the most common type of childhood diabetes. 29,000 youngsters suffer in Britain.

The team at Harvard used embryonic stem cells to produce human insulin-producing cells equivalent in almost every way to normally functioning cells in vast quantities.

Chris Mason, Professor of Regenerative Medicine, University College London, said it was potentially a major medical breakthrough.

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Cure for Type 1 diabetes imminent after Harvard stem-cell breakthrough

Four UCLA Scientists Receive Prestigious Innovator Award for Pioneering Research Using Stem Cells

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Newswise Four scientists from the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have received a National Institutes of Health (NIH) Director's New Innovator Award that will forward revolutionary stem cell and neuro-science in medicine. The four UCLA researchers were among only 50 scientists nationwide to receive the New Innovator Award, the most of any institution represented.

Each recipient received a $2.3M award for their respective projects. These included Dr. Reza Ardehali, assistant professor of cardiology, for his research investigating novel ways to use stem cells to regenerate heart tissue; Dr. Elissa Hallem, assistant professor of microbiology, immunology and molecular genetics, for her work studying interactions between animal parasites and their hosts to foster the further understanding of human parasitic diseases; Dr. Sririam Kosuri, assistant professor of chemistry and biochemistry, for his project developing new biological system technologies to solve outstanding problems in gene regulation; and Dr. Lili Yang, assistant professor of microbiology, immunology and molecular genetics, for her work developing a new method to track special immune cells for use in new cellular therapies.

"These New Innovator Award grants are an important acknowledgement of our cutting-edge research and will help our faculty drive the revolutionary advances we are seeing in stem cell and neuro-science," said Dr. Owen Witte, professor and director of the Broad Stem Cell Research Center. "Every cellular therapy that reaches patients must begin in the laboratory with novel ideas and experiments that will lead us in new directions in medicine and ultimately improve human life. That makes these awards invaluable to our research effort."

The NIH Director'sNew Innovator Award is designed specifically to support unusually creative investigators with highly innovative research ideas at an early stage of their career. The award seeks to support exceptionally creative new scientists whose research complements ongoing efforts by NIH.

Dr. Reza Ardehali: Unlocking the Secrets to Regenerating Heart Tissue

Dr. Ardehali's cutting-edge work focuses on both human embryonic stem cells and induced pluripotent stem cells, known as human pluripotent stem cells (hPSC), to provide insights into the mechanisms involved in the differentiation and specification of heart cells. hPSC have the unique ability to become any cell type in the body. His lab recently identified several novel surface markers that can highly enrich early cardiovascular progenitor cells. When delivered into functioning human hearts that are transplanted in laboratory conditions, the progenitor cells integrate structurally and functionally into the host myocardium. These studies established the basis for future hPSC-based cardiac therapy.

Dr. Ardehali and his colleagues were also the first to directly measure limited division in the cells that make up heart muscle (cardiomyocytes), proving that cardiomyocytes divide and that such cell division is rare. This discovery resolves an important controversy over whether the heart muscle has the power to regenerate and is critical for future research that may lead to regenerating heart tissue to repair damage caused by disease or heart attack.

His 2013, California Institute for Regenerative Medicine (CIRM), the state's stem cell research agency, New Faculty Physician Scientist Translational Research Award allowed Dr. Ardehali to initiate the preclinical studies on stem cell based therapies for heart disease that were pivotal for his success in the 2014 New Innovator Award competition. The NIH grant affirms the critical success of the project-to-date, and emphasizes the creativity of Dr. Ardehali's research and its potential to have a significant impact on the creation of novel regenerative approaches to treat heart disease.

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Four UCLA Scientists Receive Prestigious Innovator Award for Pioneering Research Using Stem Cells

Experts discuss new developments in the field of stem cell research and cell therapy

10.10.2014 - (idw) Fraunhofer-Gesellschaft

From 9-10 October 2014 around 200 scientists met at the Leipzig Fraunhofer Institute for Cell Therapy and Immunology for the ninth Fraunhofer Life Science Symposium. Held every two years, this year the event focused on the theme "Medicinal Cell Products and Stem Cells for Medicinal Applications". In recent years biomedical research has revealed numerous promising new approaches for the prevention and treatment of serious illnesses. The issue of stem cells plays a key role in this. With the symposium the Fraunhofer IZI offers international scientists a platform on which they can discuss the latest developments in this field.

The scientific program encompasses three major subject areas: production, manufacture and application. In the first section a paper presented by Sarah Ferber (Centre for Stem Cells, Regenerative Medicine and Tissue Engineering, Sheba Medical Center, Tel Hashomer, Israel) was one major point of interest: "Reprogramming the endocrine pancreas; autologous cell replacement therapy for diabetic patients". She spoke about the possibilities for transforming liver cells into insulin-producing cells. In the future this method could possibly be used to help patients with type 1 diabetes, where the misdirected immune system destroys the body's own insulin-producing beta cells of the pancreas.

The Fraunhofer Life Science Symposium brings together up to 200 participants from academic and clinical institutions to discuss the various focal points concerning new technologies, trends and developments. It is organized by the Fraunhofer Institute for Cell Therapy and Immunology IZI. For further information see http://www.fs-leipzig.com. Weitere Informationen:http://www.fs-leipzig.comhttp://www.izi.fraunhofer.de

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Experts discuss new developments in the field of stem cell research and cell therapy

New Stem Cell Treatment, Successful in Mice, May Someday Cure Type 1 D

When his infant son Sam was diagnosed with type 1 diabetes two decades ago, Doug Melton made himself a promise: He would cure it. When his daughter Emma was diagnosed with the same autoimmune disease at 14, he redoubled his efforts.

Finally he can see the finish line. In a paper published Thursday in the journal Cell, Melton announces that he has created a virtually unlimited supply of the cells that are missing in people with type 1 diabetes.

By replacing these cellsand then protecting them from attack by the body's immune systemMelton, now a professor and stem cell researcher at Harvard, says someday he'll have his cure.

"I think we've shown the problem can be solved," he said.

In type 1 diabetes, which usually starts in childhood and affects as many as three million Americans, the person's immune system attacks and destroys beta cells in the pancreas. Melton used stem cellswhich can turn into a wide variety of other cell typesto manufacture a new supply of these beta cells, which provide exquisitely fine-tuned responses to sugar levels in the blood.

When you eat, beta cells increase levels of insulin in your blood to process the extra sugar; when you're running on empty, the cells dial down insulin levels.

Since the 1920s, people with type 1 diabetes have been kept alive with insulin injections, though many still face nerve damage, slow wound healing, and even blindness because even the best pumps and monitors are not as effective as the body's beta cells.

The only known cure for type 1 diabetes is a beta cell transplant, which takes the cells from someone who has recently died. But the procedure is complicated, and the patient must remain on drugs forever to prevent the immune system from destroying the cells.

Fewer than 1,000 beta cell transplants have ever been done, said Albert Hwa, senior scientific program manager for beta cell therapies at the diabetes research organization JDRF, which has helped fund Melton's work for more than a decade.

Hope From Stem Cells

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New Stem Cell Treatment, Successful in Mice, May Someday Cure Type 1 D

Successful stem cell treatment in mice could one day help cure type one diabetes

On Thursday important research on stem cells and type 1 diabetes, done by professor Doug Melton, was published in the journal Cell. The results of this study have both wide and very personal implications.

Two decades ago, National Geographic reported, the current Harvard professor and stem cell researcher vowed to cure type 1 diabetes. His infant son had just been diagnosed with the disease. Professor Meltons efforts redoubled when, at age 14, his daughter was also diagnosed with the autoimmune disorder.

With the publication of this research he may have taken a step towards helping cure this disease. According to National Geographic, Melton has created a virtually unlimited supply of the cells that are missing in people with type 1 diabetes.

Type 1 diabetes, which is often diagnosed in children or young adults, affects around three million Americans. Type 1 diabetes is a chronic condition in which the pancreas produces little or no insulin, a hormone needed to allow sugar (glucose) to enter cells to produce energy, according to Mayo Clinic. This is due to the fact that the bodys immune system attacks beta cells in the pancreas, which control insulin production.

Professor Melton, along with a whole host of graduate students over 15 years, used stem cells to create replacement beta cells for mice, and human testing will begin in the next two years with government approval.

National Geographic explains:

The researchers started with cells taken from a days-old human embryo. At that point, the cells are capable of turning into any cell in the body. Others have tried to make beta cells from these human embryonic stem cells, but never fully succeeded. Meltons team spent a decade testing hundreds of combinations before finally coaxing the stem cells into becoming beta cells.

The procedure can also be done with non-embryonic stem cells, to avoid the sometimes controversial destruction of an embryo. Adult cells are turned back into stem cells and then into beta cells.

The next step is to create a protective coating for these cells so that the bodys immune system does not attack the beta cells.

MIT professor Daniel Anderson is helping Melton with a method of protection, which would work like an inkjet printer coating the cells with algae that prevents them from being attacked. This device would be implanted into patients. Two other companies are also working on strategies to coat the beta cells.

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Successful stem cell treatment in mice could one day help cure type one diabetes

Scientists Coax Human Embryonic Stem Cells Into Making Insulin

Insulin is produced by the green cells that are in clusters about the same size as the islets in the human pancreas. The red cells are producing another metabolic hormone, glucagon, that prevents low blood sugar. Harvard University hide caption

Insulin is produced by the green cells that are in clusters about the same size as the islets in the human pancreas. The red cells are producing another metabolic hormone, glucagon, that prevents low blood sugar.

A team of Harvard scientists said Thursday that they had finally found a way to turn human embryonic stem cells into cells that produce insulin. The long-sought advance could eventually lead to new ways to help millions of people with diabetes.

Right now, many people with diabetes have to regularly check the level of sugar in their blood and inject themselves with insulin to keep the sugar in their blood in check. It's an imperfect treatment.

"This is kind of a life-support for diabetics," says Doug Melton, a stem-cell researcher at Harvard Medical School. "It doesn't cure the disease and leads to devastating complications of the disease."

People with poorly controlled diabetes can suffer complications such as blindness, amputations and heart attacks.

Researchers have had some success transplanting insulin-producing cells from cadavers into people with diabetes. But it's been difficult to procure enough cells to treat large numbers of patients. So scientists have been trying to figure out how they could get more cells more easily.

For Melton, who led the work at Harvard, this has been a personal quest. His son, Sam, was diagnosed with Type 1 diabetes when he was 6 months old, and his daughter, Emma, was diagnosed with the disease when she was 14.

"I do what any parent would do, which is to say, 'I'm not going to put up with this, and I want to find a better way,' " he says.

And now Melton and his colleagues are reporting in a paper being published in this week's issue of the journal Cell that they think they have finally found that better way.

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Scientists Coax Human Embryonic Stem Cells Into Making Insulin

Fighting CP through stem cell therapy

Can brain damage caused during birth be ever reversed? Is it possible to repair the damaged brain tissues among children, who suffer from Cerebral Palsy (CP)?

So far, the treatment option for CP is to manage the symptoms of the ailment. However, in recent times, scientists and researchers worldwide have started to explore stem cell therapy as a potential treatment option for CP patients.

Can stem cells reverse the brain damage, which is the sole cause for CP among children? Our research on over 100 CP patients and stem cell therapy has been very encouraging. The patients, who underwent stem cell therapy, have displayed huge improvement in CP symptoms, says Professor and Head of Neurosurgery, LTM Medical College, Mumbai, Alok Sharma.

The neurosurgeon, who is taking part in an international conference on CP in Hyderabad this weekend, said that doctors are not concentrating on treating the brain damage.

The current treatment options available to help patients are only to mange symptoms and nobody tries to repair the underlying damage to the brain tissue. Therefore, developing a standard therapeutic approach for CP through stem cells is the need of the hour, he said.

The results from the stem cell therapy on CP patients conducted by Dr. Aloks team were recently published in Neurogens chapter on Stem cell therapy for cerebral palsy A Novel Option in a book titled Cerebral Palsy Challenges For the Future. According to the neurosurgeon, the patients after therapy had improvements in their speech, balance, upper and lower limb activity and movement.

While for stem cell research, many prefer cord blood banking, Dr. Alok pointed out that they have used stem cells from the adults derived from the bone marrow. The transplanted stem cells have the ability to migrate to the area of the damaged tissue in the brain and home-in on those affected areas to help repair the damage. Stem cells release substance that stimulates natural growth, which decreases the process of damage of the brain, Dr. Alok explained.

The researcher, who has started NeuroGen Brain and Spine Institute in Mumbai to conduct stem cell research, pointed out that stem cell therapy and other rehabilitation programmes should be encouraged for the benefit of CP patients. The positive changes that we recorded in our patients were not just restricted to their symptoms but also constructive change in brain metabolism observed through PET-CT scans, he explained. Dr. Alok Sharma can be reached at: alok276@gmail.com

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Fighting CP through stem cell therapy