These neurons derived from stem cells made from the skin of people with bipolar disorder communicated with one another differently than neurons made from the skin of people without bipolar disorder.(Credit: University of Michigan)

Bipolar disorder is known to run in families, but scientists have yet to pinpoint the genes involved. Now they have a powerful new tool in the hunt: stem cells.

In a first-of-its-kind procedure, researchers from the University of Michigan have created stem cells from the skin of people with bipolar disorder, and then coaxed the cells into neurons. This has allowed scientists, for the first time, to directly measure cellular differences between people with bipolar disorder and people without.

In the future the cells could provide a greater understanding of what causes the disease, and allow for the development of personalized medications specific to each patients cells.

The team from Michigan took skin cell samples from 22 people with bipolar disorder and 10 people without the disorder. Under carefully controlled conditions, they coaxed adult skin cells into an embryonic stem cell-like state. These cells, called induced pluripotent stem cells, then had the potential to transform into 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, study co-leader Sue OShea said in a news release.

Researchers published their findings Wednesday in the journalTranslational Psychiatry.

The research team discovered intriguing differences between stem cellsand neuronsfrom bipolar individuals and those from healthy people.

For one thing, bipolar stem cells expressed more genes associated with receiving calcium signals in the brain. Calcium signals play an important role in neuron development and function. Therefore, the new findings support the idea that genetic differences expressed early in life may contribute to the development of bipolar disorder later in life.

Once the stem cells turned into neurons, researchers tested how they reacted to lithium, a typical treatment for the disorder. The tests showed that lithium normalized the behavior of neurons from bipolar patients by altering their calcium signalingfurther confirmation that this cellular pathway should be of key interest in future studies of the disease.

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Stem Cells Shed Light on Treatments for Bipolar Disorder

11 hours ago Embryonic stem cells (ESCs) established from an interphase 2-cell SCNT blastocyst (magnification 40x). Credit: Mitalipov laboratory at OHSU

An Oregon Health & Science University scientist has been able to make embryonic stem cells from adult mouse body cells using the cytoplasm of two-cell embryos that were in the "interphase" stage of the cell cycle. Scientists had previously thought the interphase stagea later stage of the cell cyclewas incapable of converting transplanted adult cell nuclei into embryonic stem cells.

The findings by OHSU's Shoukhrat Mitalipov, Ph.D., and his team could have major implications for the science of generating patient-matched human embryonic stem cells for regenerative medicine. Human embryonic stem cells are capable of transforming into any cell type in the body. Scientists believe stem cell therapies hold promise for someday curing or treating a wide range of diseases and conditionsfrom Parkinson's disease to cardiac disease to spinal cord injuriesby replacing cells damaged through injury or illness.

Mitalipov's findings will be published March 26 in the online edition of Nature. If the new findings in mice hold true for humans, it could significantly help efforts to make rejection-proof human embryonic stem cells for regenerative therapies. That's because embryonic cells that Mitalipov's team used for reprogrammingcells in the "interphase" stageare more accessible than the traditional egg cells that are in short supply. Scientists previously had believed embryonic stem cells were capable of being produced only using the metaphase stage of egg cytoplasm.

Embryonic stem cells can be made using a process called somatic cell nuclear transfer, or SCNT, in which the nucleus from an adult cell is transferred into the cytoplasm of an unfertilized egg cell. The cytoplasmic machinery then "reprograms" that nucleus and cell into becoming an embryonic stem cell capable of transforming to any type of cell in the body.

"It has always been thought that this capacity for reprogramming ended with metaphase," said Mitalipov, senior scientist at OHSU's Oregon National Primate Research Center. "Our study shows that this reprogramming capacity remains in the later embryonic cell cytoplasm even during interphase. It looks like the factors continue working and they efficiently reprogram the cellsjust as they do in metaphase."

Many scientists have attempted to reprogram cells by interphase cytoplasm. Mitalipov and his team found success by carefully synchronizing the cell cycles of the adult cell nucleus and the recipient embryonic cytoplasm. Both had to be at an almost identical point in their respective cell cycles for the process to work, Mitalipov said.

"That was the secret," Mitalipov said. "When we did that matching, then everything worked."

Mitalipov said the next step to further his research will be to test the process in rhesus macaques.

Mitalipov has become a world scientific leader in embryonic stem cell research and in somatic cell nuclear transfer. He recently was named the director of a newly created research center at OHSUthe Center for Embryonic Cell and Gene Therapy. The center will help Mitalipov and his team accelerate their research, with expanded support from private philanthropy.

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Embryonic stem cells: Reprogramming in early embryos

Just as archeologists try to decipher ancient tablets to discern their meaning, UT Southwestern Medical Center cancer biologists are working to decode the purpose of an ancient gene considered one of the most important in cancer research.

The p53 gene appears to be involved in signaling other cells instrumental in stopping tumor development. But the p53 gene predates cancer, so scientists are uncertain what its original function is.

In trying to unravel the mystery, Dr. John Abrams, Professor of Cell Biology at UT Southwestern, and his team made a crucial new discovery -- tying the p53 gene to stem cells. Specifically, his lab found that when cellular damage is present, the gene is hyperactive in stem cells, but not in other cells. The findings suggest p53's tumor suppression ability may have evolved from its more ancient ability to regulate stem cell growth.

"The discovery was that only the stem cells light up. None of the others do. The exciting implication is that we are able to understand the function of p53 in stem cells," said Dr. Abrams, Chair of the Genetics and Development program in UT Southwestern's Graduate School of Biomedical Sciences. "We may, in fact, have some important answers for how p53 suppresses tumors."

The findings appear online in the journal eLife, a joint initiative of the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust.

p53 is one of the hardest working and most effective allies in the fight against cancer, said Dr. Abrams. It regulates other genes, marshaling them to carry out an untold number of preemptive attacks and obliterate many pre-cancerous cells before they ever pose a threat. In nearly every case where there's a tumor, p53 is damaged or deranged, strongly suggesting that it is a tumor suppressant.

Stem cells are one of the body's most useful cells because of their regenerative capabilities. Stem cells produce daughter cells, one that is a stem cell and another that can become virtually any kind of cell that's needed, such as a blood cell or a kidney cell. Stem cells have received tremendous attention in cancer research because of the stem cell hypothesis. That hypothesis maintains that malignant tumors are initiated and maintained by a population of tumor cells that have properties similar to adult stem cells.

"What this new finding tells us is that an ancient functionality of p53 was hard-wired into stem cell function," said Dr. Abrams, senior author. "From the standpoint of trying to decipher cancer biology, that's a pretty profound observation."

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The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.

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Tumor suppressor gene linked to stem cells, cancer biologists report

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

Dallas, TX (PRWEB) March 26, 2014

The Repair Stem Cells Institute (RSCI http://www.repairstemcells.org) announces its new Double Benefits for SCI stem cell treatment program specifically to benefit sufferers of Spinal Cord Injuries (SCI). The Regenerative Center, headed by Dr. Melvin M. Propis, a well-known practitioner of stem cells science, is located in Ft. Lauderdale, Florida, U.S.A. RSCIs program is by far the least expensive SCI treatment program available using real stem cells treatments within FDA regulations.

A Spinal Cord Injury (SCI) refers to any injury to the spinal cord caused by trauma rather than disease. Depending on where the spinal cord and nerve roots are damaged, the symptoms can vary widely, from pain to paralysis to incontinence. SCIs are described as "incomplete," which normally means a partial but significant paralysis, to a "complete" injury, which means a total loss of function. The number of people in the United States in 2014 who have SCI has been estimated at over a quarter million, with approximately 12,000 new cases each year.

The Repair Stem Cells Institute is the worlds only stem cell patients advocacy group whose mission is to Educate, Advocate, and Empower people to make educated choices about their medical conditions and treatments in order to lead longer and more fulfilling lives. The Double Benefits for SCI program marks a milestone in RSCIs seven years of educating thousands and guiding hundreds to adult stem cell therapies by the worlds most competent stem cells doctors at 14 affiliated international stem cell treatment centers.

Highlights of RSCIs stem cell treatment for Spinal Cord Injury include:

An RSCI Spinal Cord Injury patient, Graham Faught, who received treatment in 2013 at the Florida treatment clinic, said, This treatment literally got me back on my feet. In April, I was confined to a wheelchair with little hope. By December, I was upright again, making some progress on the treadmill and hopeful for the future. Late Flash: March 20, Graham walked 20 feet with a walker. We expect to have videos soon.

Don Margolis, founder and chairman of the Repair Stem Cells Institute (http://www.repairstemcells.org), stated, We at RSCI are very proud to offer this incredible program for SCI patients. We are confident that it will be in the forefront of many more such treatment breakthroughs. Our next target for the summer of 2014 is a double for Multiple Sclerosis, hopefully at the same price!

Currently, adult stem cell treatments are being used to help patients recover from over 150 debilitating chronic conditions previously thought to be untreatable, including the Big Three Heart Disease, Diabetes, and Cancer -- as well as Alzheimers, Parkinsons, Spinal Cord Injury, Liver Disease, Cerebral Palsy, Renal Failure, Arthritis, Autism, and Diabetes. A full list of diseases stem cells can help can be found on the RSCI website (http://www.repairstemcells.org). To date, commercial stem cell treatments have been used by over 30,000 patients with a 65% success rate.

For more information about adult stem cells, stem cell treatment, diseases stem cells can help, and the top international stem cell treatment centers, the the Repair Stem Cells Institute website offers a wealth of straightforward and unbiased information and solutions.

Contact: Don Margolis Repair Stem Cells Institute 3010 LBJ Freeway, Suite 1200 Dallas, TX 75234 Tel: (214) 556-6377 Email: info(at)repairstemcells(dot)org Website: http://www.repairstemcells.org Facebook: http://www.facebook.com/repairstemcells Twitter: http://www.twitter.com/repairstem

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The Repair Stem Cells Institute Announces Its Special Double Benefits for SCI Stem Cells Treatment Program to ...