In addition, the research demonstrates that the transplanted organ retained its immunologically privileged state during a subsequent transplantation into another naïve recipient.
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Embargo Policy: Articles for STEM CELLS and STEM CELLS Translational Medicine are embargoed for release until 9 a.m. Eastern U.S. time on the day the article is posted online. This policy applies to members of the media, authors, institutions' public information officers, and the public. Authors may not discuss their work with the media until 1 week before the mailing date or 1 week before online posting of the article, whichever is earlier, and must ensure that the media representatives agree to abide by the embargo policy. STEM CELLS Translational Medicine may refuse to publish a manuscript, despite acceptance for publication, if it has been prematurely released to the press.
“Dental cavities and inflammation of the surrounding pulp is a challenging public health issue, as tooth decay not only can cause a patient great pain but it also can lead to other serious health issues including heart disease,” explained Misako Nakashima, DDS, Ph.D., of the National Center for Geriatrics and Gerontology in Obu, Japan. “Generally we treat deep cavities by capping the tooth and removing any inflamed pulp surrounding it. But this has limited success and the problem frequently progresses until the tooth must be removed.”
But now a research team reports that it has developed a way to speed up the process. Their work, which involves the creation of a highly stable and sensitive liver stem cell model, is reported in the latest issue of STEM CELLS Translational Medicine.
“Liver toxicity is the second most common cause of human drug failure,” explained David Hay, Ph.D., of the University of Edinburgh’s MRC Centre for Regenerative Medicine, who led the team made up of university colleagues and scientists from Bristol-Myers Squibb, Princeton, N.J. “But one major bottleneck in safety testing new drugs has been finding a routine supply of good quality primary human hepatocytes from the desired genetic background.”
Researchers at the Leiden University Medical Center’s Department of Immunohematology and Blood Transfusion in Leiden, The Netherlands, led by Helene Roelofs, Ph.D., conducted the study. They were seeking an alternative to bone marrow for stem cell therapies because of the low number of stem cells available in marrow and also because harvesting them involves an invasive procedure.
“Adipose tissue is an interesting alternative since it contains approximately a 500-fold higher frequency of stem cells and tissue collection is simple,” Dr. Roelofs said.
“Moreover,” Dr. Sara M. Melief added, “400,000 liposuctions a year are performed in the U.S. alone, where the aspirated adipose tissue is regarded as waste and could be collected without any additional burden or risk for the donor.”
Many medical experts have long believed that neural stem cells (NSCs) have great potential for treating neurological diseases. However, the problem is that just a small number of NSCs can be transplanted into the brain, yielding relatively low levels of new cell growth and, thus, a limited effect. “We wanted to investigate whether using a specific population of neural cells would help increase the number of mature brain cells that the stem cell graft yields,” Dr. Wolfe explained.
The team began by harvesting NSCs from the brains of baby mice and used a process known as fluorescence activated cell sorting to identify cells with markers for CD15, a type of carbohydrate found on a cell’s surface that plays an important role in cell migration, adhesion and in the growth factor signaling involved in cell maintenance and differentiation.
“Cell transplantation strategies therefore typically introduce a stress challenge at the time of transplantation as the cells are switched from 20 percent to 3 percent oxygen, which is the average in adult organs,” she added.
A previous study had indicated that cardiac stem cells showed a better survival rate when the oxygen tension during their culturing was reduced. In this study, the Cambridge and Edinburgh teams wanted to learn if the same might prove true for neural stem cells (NSCs). So they modeled the oxygen stress that occurs during transplantation and, using NSCs collected from young rats, demonstrated that reducing the oxygen tension during culture in the laboratory from 20 percent to 3 percent resulted in significant cell death, while maintaining a 3 percent level protected them.
They saw similar results when they transplanted the stem cells into the brains of adult rats.
In fact, the dysfunction and death of RPE is thought to be behind the leading cause of blindness in the Western world — age related macular degeneration.
Transplantation of RPE cells into the retina to treat AMD has been demonstrated in animals and is now being tested in clinical trials in humans. However, protocols to generate RPE from human pluripotent stem cells are time consuming and relatively inefficient. But a team of scientists at the University of California, Santa Barbara, reports in the latest issue of STEM CELLS Translational Medicine that it has found a way to isolate RPE cells as early as 14 days following the onset of differentiation.
People who have RA overproduce a protein called tumor necrosis factor (TNF), which causes the inflammation and damage to the bones, cartilage and tissue. Anti-TNF drugs can block the action of the protein and reduce inflammation. Etanercept® (marketed under the trade name Enbrel) is a type of anti-TNF drug called a biologic that for years has been prescribed to treat RA. However, it can’t be targeted specifically to the site of the arthritis and, thus, requires higher doses that can cause serious side effects including fatal infections, multiple sclerosis, seizures, heart failure, cancer and more.
“As a result, there has been significant interest in developing RPE culture systems both to study AMD disease mechanisms and to provide substrate for possible cell-based therapies. Because of their indefinite self-renewal, human pluripotent stem cells (hPSCs) have the potential to provide an unlimited supply of RPE-like cells,” noted Donald Zack, M.D., Ph.D., who with Julien Maruotti, Ph.D., led the team of researchers from the Wilmer Institute, Johns Hopkins University School of Medicine in Baltimore, Md., and the Institute of Vision in Paris in conducting the study.
“However, most of the currently accepted methods in use for deriving RPE cells from hPSC involve time-and-labor-consuming steps done by hand, and they don’t yield large enough amount of the differentiated cells – which has posed a problem when trying to use them to develop potential new therapies,” Dr. Maruotti added.
ALS (commonly known as Lou Gehrig’s disease) is characterized by the degeneration and death of the body’s motor neurons, leading to muscle atrophy, paralysis and death due to failure of the respiratory muscles. Despite studies that have improved our understanding of how ALS develops, there are no effective treatments. However, stem cell based-therapies have emerged as a potential solution.
“The transplantation of stem-cell derived neural progenitors may have beneficial effect not only for the replacement of motor neurons already lost, but also in counteracting degeneration and death of motor neurons,” said Roland Pochet, Ph.D., of the Université libre de Bruxelles, Belgium. He headed up the research team that included scientists from INSERM et Université Paris-Sud, and the Pasteur Institute, also in Paris, and Hannover Medical School in Germany.