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February 22, 2006
Adult Stem Cell Progress Mitigates Islet Transplant Challenge
We have closely followed the research involving the transplantation of insulin-producing islets from one individual into another, hoping for a long-term and effective treatment beyond medical devices, insulin injections and medication. Although the results have been encouraging, there are a number of significant challenges that have tempered our expectations. In fact, while several hundred patients have achieved at least temporary insulin independence after receiving the islet "mini-organs" (containing insulin-producing beta cells), very few patients remain insulin independent beyond 4 years after transplantation.
On problem, in particular is that the use of conventional immunosuppressants is not feasible because of long-term side effects. Transplant recipients need to take immunosuppressive drugs that stop the immune system from rejecting the transplanted islets and, even when used, rejection remains the biggest problem. The immune system is programmed to destroy bacteria, viruses, and tissue it recognizes as "foreign," including transplanted islets. Immunosuppressive drugs are needed to keep the transplanted islets functioning. (more here)
One way to mitigate the problem is to produce beta cells from stem cells originating in the patient's own pancreas. Because the cells originate from the patients body, the immune system does not recognize them as foreign. This also has the potential for elevating the limited available of islets for transplantation.
Researchers said this week that adult stem cells in the pancreas can be transformed into insulin-producing cells. This newfound ability of endocrine progenitor stem cells in the adult human pancreas provides a major key to developing new treatments for diabetes, said researchers at the Burnham Institute for Medical Research and the Rebecca and John Moores Cancer Center at the University of California at San Diego.
Although the technology is in the feasibility stage (read many years away), and the protocols apparently involved the use of 'fetal tissue" (which we are very concerned about) the news is encouraging. Here is a related press release:
Researchers collaborating at the Burnham Institute for Medical Research and the Rebecca and John Moores Cancer Center at the University of California at San Diego have shown that endocrine progenitor stem cells exist in the adult human pancreas, and they have demonstrated that these stem cells can be transformed into insulin-producing cells. These findings, to be published in the March 1 edition of Nature Medicine, advance a major, long-range goal in developing new therapies for the treatment of diabetes, based on transplantation of insulin-producing cells and suggest a new approach to treating diabetes by transforming adult progenitor cells residing within the pancreas into insulin-producing cells.Both type 1 and type 2 diabetes are characterized by the loss and dysfunction of insulin-producing cells, also known as beta cells. Beta cells reside in the pancreatic islets, which comprise less than 2% of the pancreas. Although the success rate for islet transplantation has improved, it remains an experimental treatment for diabetes, due to the shortage of islet cells and other complications. The development of beta cell transplantation therapies is the focus of intensive study among medical scientists working on diabetes.
In the current study, researchers developed rigorous purification and cell culture techniques and used them to cull adult human pancreatic cells, incapable of producing insulin, which they termed "non-endocrine pancreatic epithelial cells", or NEPECS. To determine whether this cell population could be induced to produce insulin, they labeled the NEPECS with genetic markers and mixed them with developing pancreatic cells known to be a rich source of endocrine progenitor cells and growth factors that induce the progenitor cells' development into insulin-producing beta cells. The cells were then transplanted into mice, and after three months tissue from the mice was examined. It was found that the NEPECS labeled with the genetic marker did, in fact, include insulin-producing beta cells.
"We hypothesized that the inductive factors in developing pancreatic cells might work on cells in the adult pancreas and that turned out to be true," said Fred Levine, M.D., Ph.D., Adjunct Professor at the Burnham, project director and senior author on this paper. "We have shown, in as rigorous a manner as possible, proof-of-concept for the existence of progenitor stem insulin-producing cells within the adult human pancreas. Our proven ability to transform these progenitor stem cells into insulin-producing cells greatly expands the possibility that beta cell regeneration therapies can be developed for the treatment of diabetes. Prior to our study, it was thought that replication of beta cells arising from injury to the pancreas was the only regenerative source of beta cells in the adult pancreas. We now know that we have another, potentially more abundant, reservoir."
The team working on this project, led by Drs. Levine, Itkin-Ansari, and Mercola, indicate that the next phase of this project will focus on isolating and characterizing the growth factors that transformed NEPECS into insulin-producing, beta cells and determining whether all or a subset of the NEPECS are the progenitors of these insulin-producing beta cells.
Posted by Diabetologica at February 22, 2006 4:03 AM