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ISLET cell transplantation
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“Edmonton Protocol” Offers Hope for Diabetics
“The Edmonton Protocol” developed by James Shapiro, MD and colleagues of the university of Alberta in Edmonton, Canada involves injecting islet cells into liver via the portal vein. Rejection is prevented by using a 3-drug regimen of daclizumab plus low dose tacrolimus and sirolimus. Eight patients with Type 1 diabetes in the age group of 29 to 53 participated in the experimental protocol. Prior to islet cell transplantation all the patients had experienced severe hypoglycaemic blackouts and metabolic instability but now they have all remained insulin free for 4 to 15 months with a median of 11 months. This is an eye opener because data from the International Islet Transplant Registry found that only 12.4% of 267 islet cell transplant recipients were insulin independent beyond 1 week and just 8.2% beyond 1 year. Most patients in the Edmonton Protocol required cells from more than 1 donor organ and required 2 injections of cells to become insulin independent. All of them must continue the immunosuppressive regimen indefinitely, or life long, if necessary. The Juvenile Diabetes Foundation said that the “Edmonton Protocol is a very significant step forward in curing type 1 diabetes”. None of the 8 patients has residual diabetes by American Diabetic Association Criteria nor has anyone experienced episodes of acute rejection, diabetes related symptoms, elevations in lipid levels or other complications.
A word of caution-this therapy is appropriate only in adults who have truly failed at injected insulin treatment.
Genetic Engineering of Islet Cells could help cure Type 1 Diabetes
Genetic engineering could hold the key to a potential cure for type 1 (insulin dependent) diabetes. Shimon Efrat, PhD and colleagues at Tel Aviv University, Israel are currently studying the effects of combining cell encapsulation with the process of cell engineering. By inserting a group of genes from adenoviruses into mammalian cells, cell death (apoptosis) can be resisted. This is because these genes produce a variety of proteins that counteract apoptosis. This aspect is important because encapsulating groups of cells with a porous polymer not only allows the passage of small molecules such as nutrients and insulin but also cytokines which are triggered by cells of the immune system and can lead to apoptosis. It is hoped that if large quantities of human beta islet cell lines become available from one of several methods of manipulation, adenovirus genes could be inserted into them. It may then become possible for these encapsulated genetically engineered insulin producing islet cells to resist cell death.
Strategies to grow insulin-producing pancreatic islet cells developed
There are exciting efforts afoot to help increase transplants for diabetics and to cross the hurdle of perpetual organ donor shortage. The first is the development of the first human islet cell line that responds to glucose stimulation by secreting insulin, both in the test tube and in laboratory animals. Until now, no one has succeeded in growing large numbers of these cells in culture. This was developed by Fred Levine, MD, PhD and his fellow researchers at the University of California at San Diego Cancer Centre and announced at the American association’s Annual scientific session in San Antonio, Texas in June 2000.It opened at the possibility that human islet cell lines could be used as an unlimited source of cells for transplantation into people with diabetes.
The second-using discarded pancreatic tissue as a potential source of human islet cells. Scientists at Harvard Medical School in Boston, MA digested human pancreatic tissue that is normally discarded after isolating islets. They then grew the duct tissue in laboratory and overlaid the single epithelial cell layers with a commercially available extra cellular matrix. Over several weeks in this culture media, the cells grew, increased their insulin secretion 10 to 15 fold, and formed islet-like structures which were called cultivated human islet buds (CHIBs). When exposed to glucose, the cells increased their insulin secretion another 2-3 folds. This demonstrated that adult pancreatic duct cells could revert to multi potent cells, which could then differentiate into islet-like structures when appropriately stimulated. If vast amounts of human islet cells become available as a result of any of these approaches, transplantation could be extended to persons with type 2 diabetes (non insulin dependent) in addition to those with type 1 diabetes.
Available at:
https://www.itnnews.co.in/indian-transplant-newsletter/issue7/ISLET-cell-transplantation-162.htm
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