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

'Stem Cell Tourism' Takes Advantage of Patients, Says Law Professor

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Newswise MADISON, Wis. Desperate patients are easy prey for unscrupulous clinics offering untested and risky stem cell treatments, says law and bioethics Professor Alta Charo of the University of Wisconsin-Madison, who is studying stem cell tourism.

Stem cells are cells that can form many types of cells in the body, and that makes them inherently promising and dangerous. Stem cell tourism refers to people traveling, both within the U.S. and abroad, in pursuit of advertised stem cell therapies to purportedly treat a variety of medical conditions.

The evidence for therapeutic use of stem cells is very limited, except for bone marrow stem cells, but patients all over the world are convinced stem cells will cure their disease, says Charo. While there are some very promising results in the early clinical trials for stem cell therapies using embryonic and other kinds of stem cells, the treatments being advertised by these clinics are dubious, mostly ineffective, and sometimes positively harmful.

Patients are being hoodwinked, but there are dilemmas about tackling (the treatments) at regulatory or political levels.

The outrage over failures in stem cell tourism is limited, Charo says. Patients may pay tens of thousands of dollars for procedures that may carry no promise of success or carry grievous risks of failure. Most people have no reason to pay attention, and those who are paying attention are sick, so they are focused on trying anything, Charo says. If it does not work, they are already in a bad position with plenty to think about.

During a search for stem cell therapies on the web, Charo found products that supposedly enhance the natural formation of stem cells in the skin alongside approved and unapproved treatments in the United States, and stem cell clinics outside the United States, like a stem cell treatment for spinal conditions that might be innocuous, but is probably useless.

Some American operators are trying to slip through Food and Drug Administration regulation, says Charo, who served as senior policy advisor in the Office of the Commissioner of the FDA between 2009 and 2011. The FDA regulates medical devices, tissue transplants and drugs, but not organ transplants or the way medicine is practiced.

To sell a product that can heal without claiming it is a drug, some clinics remove stem cells from a patient, grow them with minimal manipulation, and then reinsert the resulting cells back to the same patient. There has been a long-running battle over whether that is a tissue transplant akin to organ transplantation and thus the practice of medicine, or a tissue transplant that is acting like drug, Charo says. If the latter, then what you do is subject to FDA [regulation], so you have to prove that your product is safe and effective, which almost always requires expensive clinical trials.

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'Stem Cell Tourism' Takes Advantage of Patients, Says Law Professor

New Method Makes Muscle Cells From Human Stem Cells

March 24, 2014

Image Caption: Muscle cells are stained green in this micrograph of cells grown from embryonic stem cells in the lab of Masatoshi Suzuki at the University of Wisconsin -- Madison. Cell nuclei are stained blue; the muscle fibers contain multiple nuclei. Nuclei outside the green fibers are from non-muscle cells. Suzuki has developed a new method of growing stem cells into muscle cells that could be more suitable for treating disease. Suzuki hopes to experiment next with animals that model muscular dystrophy and amyotrophic lateral sclerosis. Credit: Masatoshi Suzuki

David Tenenbaum, University of Wisconsin-Madison

As stem cells continue their gradual transition from the lab to the clinic, a research group at the University of Wisconsin-Madison has discovered a new way to make large concentrations of skeletal muscle cells and muscle progenitors from human stem cells.

The new method, described in the journal Stem Cells Translational Medicine, could be used to generate large numbers of muscle cells and muscle progenitors directly from human pluripotent stem cells. These stem cells, such as embryonic (ES) or induced pluripotent stem (iPS) cells, can be made into virtually any adult cell in the body.

Adapting a method previously used to make brain cells, Masatoshi Suzuki, an assistant professor of comparative biosciences in the School of Veterinary Medicine, has directed those universal stem cells to become both adult muscle cells and muscle progenitors.

Importantly, the new technique grows the pluripotent stem cells as floating spheres in high concentrations of two growth factors, fibroblast growth factor-2 and epidermal growth factor. These growth factors urge the stem cells to become muscle cells.

Researchers have been looking for an easy way to efficiently differentiate stem cells into muscle cells that would be allowable in the clinic, says Suzuki. The novelty of this technique is that it generates a larger number of muscle stem cells without using genetic modification, which is required by existing methods for making muscle cells.

Many other protocols have been used to enhance the number of cells that go to a muscle fate, says co-author Jonathan Van Dyke, a post-doctoral fellow in Suzukis laboratory. But whats exciting about the new protocol is that we avoid some techniques that would prohibit clinical applications. We think this new method has great promise for alleviating human suffering.

Last year, Suzuki demonstrated that transplants of another type of human stem cells somewhat improved survival and muscle function in rats that model amyotrophic lateral sclerosis (ALS). Also known as Lou Gehrigs disease, ALS destroys nerves and causes a loss of muscle control. The muscle progenitors generated with Suzukis new method could potentially play a similar role but with enhanced effect.

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New Method Makes Muscle Cells From Human Stem Cells

New way to make muscle cells from human stem cells

As stem cells continue their gradual transition from the lab to the clinic, a research group at the University of Wisconsin-Madison has discovered a new way to make large concentrations of skeletal muscle cells and muscle progenitors from human stem cells.

The new method, described in the journal Stem Cells Translational Medicine, could be used to generate large numbers of muscle cells and muscle progenitors directly from human pluripotent stem cells. These stem cells, such as embryonic (ES) or induced pluripotent stem (iPS) cells, can be made into virtually any adult cell in the body.

Adapting a method previously used to make brain cells, Masatoshi Suzuki, an assistant professor of comparative biosciences in the School of Veterinary Medicine, has directed those universal stem cells to become both adult muscle cells and muscle progenitors.

Importantly, the new technique grows the pluripotent stem cells as floating spheres in high concentrations of two growth factors, fibroblast growth factor-2 and epidermal growth factor. These growth factors "urge" the stem cells to become muscle cells.

"Researchers have been looking for an easy way to efficiently differentiate stem cells into muscle cells that would be allowable in the clinic," says Suzuki. The novelty of this technique is that it generates a larger number of muscle stem cells without using genetic modification, which is required by existing methods for making muscle cells.

"Many other protocols have been used to enhance the number of cells that go to a muscle fate," says co-author Jonathan Van Dyke, a post-doctoral fellow in Suzukis laboratory. "But what's exciting about the new protocol is that we avoid some techniques that would prohibit clinical applications. We think this new method has great promise for alleviating human suffering."

Last year, Suzuki demonstrated that transplants of another type of human stem cells somewhat improved survival and muscle function in rats that model amyotrophic lateral sclerosis (ALS). Also known as Lou Gehrig's disease, ALS destroys nerves and causes a loss of muscle control. The muscle progenitors generated with Suzukis new method could potentially play a similar role but with enhanced effect.

The new technique can also be used to grow muscle cells from iPS cells from patients with neuromuscular diseases like ALS, spinal muscular atrophy and muscular dystrophy. Thus, the technique could produce adult muscle cells in a dish that carry genetic diseases. These cells could then be used as a tool for studying these diseases and screening potential drug compounds, says Suzuki. "Our protocol can work in multiple ways and so we hope to provide a resource for people who are exploring specific neuromuscular diseases in the laboratory."

The new protocol incorporates a number of advantages. First, the cells are grown in defined supplements without animal products such as bovine serum, enhancing the clinical safety for the muscle stem cells. Second, when grown as spheres, the cells grow faster than with previous techniques. Third, 40 to 60 percent of the cells grown using the process are either muscle cells or muscle progenitors, a high proportion compared to traditional non-genetic techniques of generating muscle cells from human ES and iPS cells.

Suzuki and his group hope that by further manipulating the chemical environment of the spheres of stem cells, they may increase that number, further easing the path toward human treatment.

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New way to make muscle cells from human stem cells

Wounded Pa. soldier seeks Chinese stem cell cure

YORK, Pa. (AP) - A York County soldier left partially paralyzed when he was shot in Afghanistan nearly two years ago is banking on stem cells to help him regain movement.

Matthew Hanes, 22, of Manchester Township will head to China in April to undergo surgery to repair part of his damaged spinal cord.

Doctors essentially will use minor surgery and stem cell therapy to build a bridge over two vertebrae that were shattered when Hanes was shot.

At the minimum Ill get at least some feeling back where I dont have it in certain places, but I could get everything back if it goes well, Hanes said.

U.S. Army Cpl. Hanes was shot while on patrol in Afghanistan in June 2012. He was left with limited use of his upper body and no use of his lower extremities.

RESEARCH: Soon after he returned to the U.S., Hanes began researching stem cell therapy as possible treatment.

Thats how he found Puhua International Hospital in Beijing, where he will fly on April 1 for the treatment. Hes slated to return stateside later that month.

Its coming up slowly now that I know its on, Hanes said.

During his research, Hanes said he found the U.S. is so far behind on stem cell research compared to some countries in Asia, such as China, and Europe.

For years, the federal government imposed tight restrictions on stem cell research until it was loosened in 2009 by President Barrack Obama.

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Wounded Pa. soldier seeks Chinese stem cell cure

Arthritic shoulders; Len discusses his results 9 months after stem cell therapy by Dr Harry Adelson – Video


Arthritic shoulders; Len discusses his results 9 months after stem cell therapy by Dr Harry Adelson
Arthritic shoulders; Len discusses his results 9 months after stem cell therapy by Dr Harry Adelson http://www.docereclinics.com.

By: Harry Adelson, N.D.

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Arthritic shoulders; Len discusses his results 9 months after stem cell therapy by Dr Harry Adelson - Video

The furor over fresh-cell therapy (which is NOT stem cell therapy)

The Philippines is the biggest market for the popular, if highly controversial, alternative treatment in Germany called fresh-cell therapy (FCT). Fresh cells derived from the fetus of an unborn lamb are injected into patients, and are said to cure a large number of illnesses.

Despite the high cost of the treatment, wealthy Filipinos are undeterred, and typically arrive in droves in a sleepy town outside Frankfurt, their hopes of being cured or rejuvenated pinned on the life of every donor sheep.

Given its renown, its no surprise that questions about the efficacy and safety of FCT has been the subject of discussions among health professionals. There have also been rumors of deaths after FCT.

The proponents of FCT in Germany, however, claim that all talk about patient deaths and questionable safety standards are unfounded, and an uncouth effort to discredit FCT so that the same medical professionals here could promote stem-cell therapy, which is allowed in the country. They deny the rumors of deaths and challenge their accusers to show proof. They also maintain that FCT is a decades-old, legitimate and safe naturopathic treatment.

Theres also a rivalry in Edenkoben between the famous clinic Villa Medica and the breakaway practice of Dr. Robert Janson-Mller, who used to work at the same clinic.

Dr. Mller now administers FCT in a hotel, which doubles as his clinic. This gave rise to talks questioning the standards of a practice that is done in a hotel, not a hospital. Some accounts also say that there have been Filipino patients fooled into believing they were bound for Villa Medica, only to find themselves in Dr. Mullers hotel.

Inquirer Lifestyle visits the two rival clinics in Germany, and we experience firsthand what FCT is all about.

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The furor over fresh-cell therapy (which is NOT stem cell therapy)

Stem cell findings may offer answers for some bladder defects and disease

PUBLIC RELEASE DATE:

21-Mar-2014

Contact: Charles Casey charles.casey@ucdmc.ucdavis.edu 916-734-9048 University of California - Davis Health System

(SACRAMENTO, Calif.) For the first time, scientists have succeeded in coaxing laboratory cultures of human stem cells to develop into the specialized, unique cells needed to repair a patient's defective or diseased bladder.

The breakthrough, developed at the UC Davis Institute for Regenerative Cures and published today in the scientific journal Stem Cells Translational Medicine, is significant because it provides a pathway to regenerate replacement bladder tissue for patients whose bladders are too small or do not function properly, such as children with spina bifida and adults with spinal cord injuries or bladder cancer.

"Our goal is to use human stem cells to regenerate tissue in the lab that can be transplanted into patients to augment or replace their malfunctioning bladders," said Eric Kurzrock, professor and chief of the division of pediatric urologic surgery at UC Davis Children's Hospital and lead scientist of the study, which is titled "Induction of Human Embryonic and Induced Pluripotent Stem Cells into Urothelium."

To develop the bladder cells, Kurzrock and his UC Davis colleagues investigated two categories of human stem cells. In their key experiments, they used induced pluripotent stem cells (iPS cells), which were derived from lab cultures of human skin cells and umbilical blood cells that had been genetically reprogrammed to convert to an embryonic stem cell-like state.

If additional research demonstrates that grafts of bladder tissue grown from human stem cells will be safe and effective for patient care, Kurzrock said that the source of the grafts would be iPS cells derived from a patient's own skin or umbilical cord blood cells. This type of tissue would be optimal, he said, because it lowers the risk of immunological rejection that typifies most transplants.

In their investigation, Kurzrock and his colleagues developed a protocol to prod the pluripotent cells into becoming bladder cells. Their procedure was efficient and, most importantly, the cells proliferated over a long period of time a critical element in any tissue engineering application.

"What's exciting about this discovery is that it also opens up an array of opportunities using pluripotent cells," said Jan Nolta, professor and director of the UC Davis Stem Cell program and a co-author on the new study. "When we can reliably direct and differentiate pluripotent stem cells, we have more options to develop new and effective regenerative medicine therapies. The protocols we used to create bladder tissue also provide insight into other types of tissue regeneration."

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Stem cell findings may offer answers for some bladder defects and disease

Stem cell findings may offer answers for some bladder defects, disease

For the first time, scientists have succeeded in coaxing laboratory cultures of human stem cells to develop into the specialized, unique cells needed to repair a patient's defective or diseased bladder.

The breakthrough, developed at the UC Davis Institute for Regenerative Cures and published today in the scientific journal Stem Cells Translational Medicine, is significant because it provides a pathway to regenerate replacement bladder tissue for patients whose bladders are too small or do not function properly, such as children with spina bifida and adults with spinal cord injuries or bladder cancer.

"Our goal is to use human stem cells to regenerate tissue in the lab that can be transplanted into patients to augment or replace their malfunctioning bladders," said Eric Kurzrock, professor and chief of the division of pediatric urologic surgery at UC Davis Children's Hospital and lead scientist of the study, which is titled "Induction of Human Embryonic and Induced Pluripotent Stem Cells into Urothelium."

To develop the bladder cells, Kurzrock and his UC Davis colleagues investigated two categories of human stem cells. In their key experiments, they used induced pluripotent stem cells (iPS cells), which were derived from lab cultures of human skin cells and umbilical blood cells that had been genetically reprogrammed to convert to an embryonic stem cell-like state.

If additional research demonstrates that grafts of bladder tissue grown from human stem cells will be safe and effective for patient care, Kurzrock said that the source of the grafts would be iPS cells derived from a patient's own skin or umbilical cord blood cells. This type of tissue would be optimal, he said, because it lowers the risk of immunological rejection that typifies most transplants.

In their investigation, Kurzrock and his colleagues developed a protocol to prod the pluripotent cells into becoming bladder cells. Their procedure was efficient and, most importantly, the cells proliferated over a long period of time -- a critical element in any tissue engineering application.

"What's exciting about this discovery is that it also opens up an array of opportunities using pluripotent cells," said Jan Nolta, professor and director of the UC Davis Stem Cell program and a co-author on the new study. "When we can reliably direct and differentiate pluripotent stem cells, we have more options to develop new and effective regenerative medicine therapies. The protocols we used to create bladder tissue also provide insight into other types of tissue regeneration."

UC Davis researchers first used human embryonic stem cells obtained from the National Institutes of Health's repository of human stem cells. Embryonic stem cells can become any cell type in the body (i.e., they are pluripotent), and the team successfully coaxed these embryonic stem cells into bladder cells. They then used the same protocol to coax iPS cells made from skin and umbilical cord blood into bladder cells, called urothelium, that line the inside of the bladder. The cells expressed a very unique protein and marker of bladder cells called uroplakin, which makes the bladder impermeable to toxins in the urine.

The UC Davis researchers adjusted the culture system in which the stem cells were developing to encourage the cells to proliferate, differentiate and express the bladder protein without depending upon signals from other human cells, said Kurzrock. In future research, Kurzrock and his colleagues plan to modify the laboratory cultures so that they will not need animal and human products, which will allow use of the cells in patients.

Kurzrock's primary focus as a physician is with children suffering from spina bifida and other pediatric congenital disorders. Currently, when he surgically reconstructs a child's defective bladder, he must use a segment of their own intestine. Because the function of intestine, which absorbs food, is almost the opposite of bladder, bladder reconstruction with intestinal tissue may lead to serious complications, including urinary stone formation, electrolyte abnormalities and cancer. Developing a stem cell alternative not only will be less invasive, but should prove to be more effective, too, he said.

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Stem cell findings may offer answers for some bladder defects, disease