Scientists Use Stem Cells to Study Bipolar Disorder

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TUESDAY, March 25, 2014 (HealthDay News) -- Brain cells of patients with bipolar disorder act differently than those of people without the mental illness, according to scientists who conducted a stem cell study of the condition.

The investigators said their research might one day lead to a better understanding of bipolar disorder and new treatments for the disease, which causes extreme emotional highs and lows. About 200 million people worldwide have bipolar disorder.

"We're very excited about these findings. But we're only just beginning to understand what we can do with these cells to help answer the many unanswered questions in bipolar disorder's origins and treatment," said study co-leader Dr. Melvin McInnis, a professor of bipolar disorder and depression at the University of Michigan Medical School.

The study authors took skin stem cells from people with and without bipolar disorder and transformed them into neurons similar to brain cells. It's the first time that stem cell lines specific to bipolar disorder have been created, the researchers said.

They discovered distinct differences in how the two sets of neurons behave and communicate with each other. The cells also differed in their response to lithium, the most widely used treatment for bipolar disorder.

The study was published online March 25 in the journal Translational Psychiatry.

"This gives us a model that we can use to examine how cells behave as they develop into neurons," study co-leader Sue O'Shea, a professor in the department of cell and developmental biology and director of the University of Michigan Pluripotent Stem Cell Research Lab, said in a university news release.

"Already, we see that cells from people with bipolar disorder are different in how often they express certain genes, how they differentiate into neurons, how they communicate, and how they respond to lithium," O'Shea said.

McInnis said it's possible the research could lead to new types of drug trials. If it becomes possible to test new drug candidates in these cells, patients would be spared the current trial-and-error approach that leaves many with uncontrolled symptoms, he said.

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Scientists Use Stem Cells to Study Bipolar Disorder

Stem Cells Shed Light On Bipolar Disease

Researchers have grown embryonic-like stem cells from patients with bipolar disorder and transformed them into brain cells that are already answering questions about the condition.

The cells, which carry the precisely tailored genetic instructions from the patients own cells, behave differently than cells taken from people without the disorder, the researchers report.

Already, we see that cells from people with bipolar disorder are different in how often they express certain genes, how they differentiate into neurons, how they communicate, and how they respond to lithium," Sue O'Shea, a stem cell specialist at the University of Michigan who led the study, said in a statement.

The work, described in the journal Translational Psychiatry, helps fulfill one of the big promises of stem cells research using a patients own cells to study his or her disease.

Mental illness is especially hard to study. Getting into a living persons brain is almost impossible, and scientists cant deliberately cause it in people in order to study it.

Creating animals such as mice with what looks like human mental illness is imprecise at best.

The University of Michigan team turned instead to what are called induced pluripotent stem cells, or iPS cells. These are ordinary skin cells taken from a patient and tricked into turning back into the state of a just-conceived embryo.

These cells, grown from skin cells taken from people with bipolar disorder, arose from stem cells and were coaxed to become neural progenitor cells -- the kind that can become any sort of nervous system cell. The research showed differences in cell behavior compared with cells grown from people without bipolar disorder.

They are pluripotent, meaning they can become any type of cell there is. In this case, the Michigan team redirected the cells to become neurons the cells that make up much of the brain. "This gives us a model that we can use to examine how cells behave as they develop into neurons, OShea said.

Bipolar disorder, once called manic-depression, is very common, affecting an estimated 3 percent of the population globally. It runs in families, suggesting a strong genetic cause, and is marked by mood swings from depression to feelings of euphoria and creativity thats considered the manic phase.

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Stem Cells Shed Light On Bipolar Disease

Stem Cells Shed Light on Bipolar Disorder

Researchers have grown embryonic-like stem cells from patients with bipolar disorder and transformed them into brain cells that are already answering questions about the condition.

The cells, which carry the precisely tailored genetic instructions from the patients own cells, behave differently than cells taken from people without the disorder, the researchers report.

Already, we see that cells from people with bipolar disorder are different in how often they express certain genes, how they differentiate into neurons, how they communicate, and how they respond to lithium," Sue O'Shea, a stem cell specialist at the University of Michigan who led the study, said in a statement.

The work, described in the journal Translational Psychiatry, helps fulfill one of the big promises of stem cells research using a patients own cells to study his or her disease.

Mental illness is especially hard to study. Getting into a living persons brain is almost impossible, and scientists cant deliberately cause it in people in order to study it.

Creating animals such as mice with what looks like human mental illness is imprecise at best.

The University of Michigan team turned instead to what are called induced pluripotent stem cells, or iPS cells. These are ordinary skin cells taken from a patient and tricked into turning back into the state of a just-conceived embryo.

These cells, grown from skin cells taken from people with bipolar disorder, arose from stem cells and were coaxed to become neural progenitor cells -- the kind that can become any sort of nervous system cell. The research showed differences in cell behavior compared with cells grown from people without bipolar disorder.

They are pluripotent, meaning they can become any type of cell there is. In this case, the Michigan team redirected the cells to become neurons the cells that make up much of the brain. "This gives us a model that we can use to examine how cells behave as they develop into neurons, OShea said.

Bipolar disorder, once called manic-depression, is very common, affecting an estimated 3 percent of the population globally. It runs in families, suggesting a strong genetic cause, and is marked by mood swings from depression to feelings of euphoria and creativity thats considered the manic phase.

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Stem Cells Shed Light on Bipolar Disorder

Replacing insulin through stem cell-derived pancreatic cells under the skin

PUBLIC RELEASE DATE:

24-Mar-2014

Contact: Susan Gammon Ph.D. sgammon@sanfordburnham.org 858-795-5012 Sanford-Burnham Medical Research Institute

LA JOLLA, Calif., March 25, 2014 Sanford-Burnham Medical Research Institute (Sanford-Burnham) and UC San Diego School of Medicine scientists have shown that by encapsulating immature pancreatic cells derived from human embryonic stem cells (hESC), and implanting them under the skin in animal models of diabetes, sufficient insulin is produced to maintain glucose levels without unwanted potential trade-offs of the technology. The research suggests that encapsulated hESC-derived insulin-producing cells hold great promise as an effective and safe cell-replacement therapy for insulin-dependent diabetes.

"Our study critically evaluates some of the potential pitfalls of using stem cells to treat insulin-dependent diabetes," said Pamela Itkin-Ansari, Ph.D., adjunct assistant professor in the Development, Aging, and Regenerative Program at Sanford-Burnham, with a joint appointment at UC San Diego.

"We have shown that encapsulated hESC-derived pancreatic cells are able to produce insulin in response to elevated glucose without an increase in the mass or their escape from the capsule. These results are important because it means that the encapsulated cells are both fully functional and retrievable," said Itkin-Ansari.

In the study, published online in Stem Cell Research, Itkin-Ansari and her team used bioluminescent imaging to see if encapsulated cells stay in the capsule after implantation.

Previous attempts to replace insulin-producing cells, called beta cells, have met with significant challenges. For example, researchers have tried treating diabetics with mature beta cells, but because mature cells are fragile and scarce, the method is fraught with problems. Moreover, since the cells come from organ donors, they may be recognized as foreign by the recipient's immune systemrequiring patients to take immunosuppressive drugs to prevent their immune system from attacking the donor's cells, ultimately leaving patients vulnerable to infections, tumors, and other adverse events.

Encapsulation technology was developed to protect donor cells from exposure to the immune systemand has proven extremely successful in preclinical studies.

Itkin-Ansari and her research team previously made an important contribution to the encapsulation approach by showing that pancreatic islet progenitor cells are an optimal cell type for encapsulation. They found that progenitor cells were more robust than mature beta cells to encapsulate, and while encapsulated, they matured into insulin-producing cells, which secreted insulin only when needed.

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Replacing insulin through stem cell-derived pancreatic cells under the skin

Stem cell trials on tackling osteoarthritis may lead to treatment in five years

The trials involve injecting adult stem cells derived from adipose tissue or fat into cartilage to stimulate its regeneration

Researchers in Galway predict that stem cells could be used to treat osteoarthritis within five years, following successful initial clinical trials.

The trials involve injecting adult stem cells derived from adipose tissue or fat into cartilage to stimulate its regeneration.

Osteoarthritis affects some 70 million people across the EU, and current treatment is limited to surgery or pain management.

Some 400,000 people in Ireland are affected by this most common form of human arthritis, which is characterised by the often very painful degeneration of cartilage in joints.

Successful trial NUI Galway (NUIG) scientists, who are part of a 9 million EU-funded project, have just finished the successful phase one clinical trial.

Prof Frank Barry, scientific director of NUIGs Regenerative Medicine Institute (Remedi), yesterday said the positive early results indicate a treatment was in sight.

From the clinical trials conducted so far, we have seen the first signs of finding a cure for this truly incapacitating disease which affects so many, Prof Barry said. Using the patients own stem cells we have been able to treat their diseased joints, and relieve their suffering and burden of pain.

Whilst we are still in the early stages of clinical trials, the results so far are extremely positive such that the use of stem cell therapy for osteoarthritis could become a reality for patients within the next five years, he said.

Adipose stem cells Stem cells can be harvested in large quantities from adipose tissue or fat, with minimally invasive surgery. These cells have emerged in recent years as a good alternative to stem cells derived from bone marrow, Prof Barry notes.

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Stem cell trials on tackling osteoarthritis may lead to treatment in five years

First Stem Cell Study of Bipolar Disorder Yields Promising Results

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Newswise ANN ARBOR, Mich. What makes a person bipolar, prone to manic highs and deep, depressed lows? Why does bipolar disorder run so strongly in families, even though no single gene is to blame? And why is it so hard to find new treatments for a condition that affects 200 million people worldwide?

New stem cell research published by scientists from the University of Michigan Medical School, and fueled by the Heinz C. Prechter Bipolar Research Fund, may help scientists find answers to these questions.

The team used skin from people with bipolar disorder to derive the first-ever stem cell lines specific to the condition. In a new paper in Translational Psychiatry, they report how they transformed the stem cells into neurons, similar to those found in the brain and compared them to cells derived from people without bipolar disorder.

The comparison revealed very specific differences in how these neurons behave and communicate with each other, and identified striking differences in how the neurons respond to lithium, the most common treatment for bipolar disorder.

Its the first time scientists have directly measured differences in brain cell formation and function between people with bipolar disorder and those without.

The researchers are from the Medical Schools Department of Cell & Developmental Biology and Department of Psychiatry, and U-Ms Depression Center.

Stem cells as a window on bipolar disorder The team used a type of stem cell called induced pluripotent stem cells, or iPSCs. By taking small samples of skin cells and exposing them to carefully controlled conditions, the team coaxed them to turn into stem cells that held the potential to become any type of cell. With further coaxing, the cells became neurons.

This gives us a model that we can use to examine how cells behave as they develop into neurons. Already, we see that cells from people with bipolar disorder are different in how often they express certain genes, how they differentiate into neurons, how they communicate, and how they respond to lithium, says Sue OShea, Ph.D., the experienced U-M stem cell specialist who co-led the work.

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First Stem Cell Study of Bipolar Disorder Yields Promising Results

First stem cell study of bipolar disorder offers hope for …

When it comes to understanding bipolar disorder, many questions remain unanswered such as what truly causes the condition and why finding proper treatments is so difficult.

But now, researchers have taken a huge step towards solving some of the disorders complex mysteries.

Through groundbreaking stem cell research, scientists from the University of Michigan Medical School and the Heinz C. Prechter Bipolar Researcher Fund transformed skin cells from people with bipolar disorder into neurons that mimicked those found in their brains. They were then able to compare these nerve stem cells with cells derived from people without bipolar disorder and study how the neurons responded to medications for the condition.

Detailed in the journal Translational Psychiatry, this study marks the first time researchers have derived a stem cell line specific to bipolar disorder.

Once we have derived nerve cells, were able to study those cells and determine how they behave compared to other cells and how they behave in response to medications, principal investigator Dr. Melvin McInnis, of the Prechter Bipolar Research Fund, told FoxNews.com. So if we can understand the basic biological problems with these cells, we can potentially identify interventions that further how we understand the illness and how we treat it.

Also known as manic-depressive illness, bipolar disorder is a brain condition characterized by intense shifts in mood alternating between periods of high energy and mania to periods of severe anxiety and depression. While the condition is known to run in families, scientists still arent fully certain what causes its development, believing it to be a combination of genetics and other factors.

Additionally, the most common form of treatment for the disorder, lithium, is also somewhat of a mystery.

We really do not know and understand what drives these fluctuations in moods; we dont understand how the medications truly work that help individuals with variability in their moods, McInnis said. We dont know why an individual will become ill at a particular time. All we know is really at an observational level.

In order to better understand what is happening in the bipolar mind, McInnis and his team took small samples of skin from individuals who had been diagnosed with bipolar disorder. These samples were then exposed to specific growth factors, which coaxed the cells into becoming induced pluripotent stem cells (iPSCs) meaning they had the ability to turn into any type of cell. Subsequently, the cells were exposed to an additional set of growth factors, which coaxed them into becoming neurons.

This process has also been used to better understand other complex brain disorders, such as schizophrenia and conditions that cause seizures. According to McInnis, the technique allows researchers to examine how cells behave as they develop into a whole new type of cell, as well as how they function when they finally become neurons.

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First stem cell study of bipolar disorder offers hope for ...

First stem cell study of bipolar disorder yields promising …

PUBLIC RELEASE DATE:

25-Mar-2014

Contact: Kara Gavin kegavin@umich.edu 734-764-2220 University of Michigan Health System

ANN ARBOR, Mich. What makes a person bipolar, prone to manic highs and deep, depressed lows? Why does bipolar disorder run so strongly in families, even though no single gene is to blame? And why is it so hard to find new treatments for a condition that affects 200 million people worldwide?

New stem cell research published by scientists from the University of Michigan Medical School, and fueled by the Heinz C. Prechter Bipolar Research Fund, may help scientists find answers to these questions.

The team used skin from people with bipolar disorder to derive the first-ever stem cell lines specific to the condition. In a new paper in Translational Psychiatry, they report how they transformed the stem cells into neurons, similar to those found in the brain and compared them to cells derived from people without bipolar disorder.

The comparison revealed very specific differences in how these neurons behave and communicate with each other, and identified striking differences in how the neurons respond to lithium, the most common treatment for bipolar disorder.

It's the first time scientists have directly measured differences in brain cell formation and function between people with bipolar disorder and those without.

The researchers are from the Medical School's Department of Cell & Developmental Biology and Department of Psychiatry, and U-M's Depression Center.

Stem cells as a window on bipolar disorder

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First stem cell study of bipolar disorder yields promising ...

Adjustable scaffold tunes stem cell growth

A new scaffold material based on a biocompatible silk-alginate hydrogel, which can be made soft or stiff, could provide the just right environment to culture stem cells for regenerative medicine, say researchers.

Stem cells could provide powerful new treatments for intractable autoimmune diseases, cancer, and other conditions. But the use of stem cells in the clinic requires a robust and reliable culture system that mimics the natural microenvironment of the cell. This microenvironment provides crucial direction to the function and viability of stem cells but is tricky to recreate artificially.

The complex make-up of the microenvironment, which includes a network of proteins like collagen or elastins forming an extracellular matrix (ECM), decides the fate of stem cells through a number of different, complementary mechanisms. For example, the stiffness of the matrix, determined by the orientation and elasticity of the fibers making up the ECM, as well as its fluid handling properties, the presence of signaling molecules and the creation of cytokine gradients all have a profound effect on the growing stem cells.

The new silk-alginate biocomposite developed by researchers at Stanford University and Queens University in Canada could provide a simple solution to tackle these complex problems. The hydrogel is formed from a mixture of alginate and silk in solution, which rapidly gels when immersed in CaCl2 [Ziv, et al., Biomaterials 35 (2014) 3736-3743, http://dx.doi.org/10.1016/j.biomaterials.2014.01.029%5D. But crucially, the stable hydrogel can be made soft and flexible or stiff by controlling the silk-alginate ratio and the concentration of crosslinking ions. Varying the silk-alginate ratio during fabrication changes the elasticity of the hydrogel, which can determine the yield of a particular differentiation path. The elasticity can be further fine-tuned in vitro by varying the CaCl2 concentration. Being able to modify the stiffness of the scaffold material to such a degree gives researchers a powerful means of guiding stem cell survival and differentiation.

The ability to change the elasticity [of the silk-alginate hydrogel] helps mimic the natural process that is happening in the stem cell niche and improves the stem cell commitment into desired differentiation paths, explains first author Keren Ziv, of the Molecular Imaging Program at Stanford.

Using the protein laminin to enhance cell adhesion and promote cell growth, the researchers cultured mouse embryonic stem cells in the new scaffold material and transplanted samples into live mice. The silk-alginate hydrogel appears to be better at maintaining the survival of stem cells once transplanted than the best current alternative, matrigel.

But there is a long way to go until the new scaffold material could be used in the clinic for stem cell applications, cautions Ziv. Ideally, such applications would require the injection of the hydrogel in liquid form followed by gelation but this is currently unfeasible in vivo. The long-term stability of the hydrogel also needs to be scrutinized, along with its effect on other cell types. These issues are tractable, however, say the researchers, and are the focus of on-going efforts.

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Adjustable scaffold tunes stem cell growth