Islet Transplantation (Continued)
Rejection is the biggest problem with any transplant. The immune system is programmed to destroy bacteria, viruses, and tissue it recognizes as "foreign," including transplanted islets. In addition, the autoimmune response that destroyed transplant recipients' own islets in the first place can recur and attack the transplanted islets. Immunosuppressive drugs are needed to keep the transplanted islets functioning.
The Edmonton protocol introduced the use of a new combination of immunosuppressive drugs, also called anti-rejection drugs, including daclizumab (Zenapax), sirolimus (Rapamune), and tacrolimus (Prograf). Daclizumab is given intravenously right after the transplant and then discontinued. Sirolimus and tacrolimus, the two main drugs that keep the immune system from destroying the transplanted islets, must be taken for life or for as long as the islets continue to function. These drugs have significant side effects and their long-term effects are still not fully known. Immediate side effects of immunosuppressive drugs may include mouth sores and gastrointestinal problems, such as stomach upset and diarrhea. Patients may also have increased blood cholesterol levels, hypertension, anemia, fatigue, decreased white blood cell counts, decreased kidney function, and increased susceptibility to bacterial and viral infections. Taking immunosuppressive drugs also increases the risk of tumors and cancer.
Researchers continue to develop and study modifications to the Edmonton protocol drug regimen, including the use of new drugs and new combinations of drugs designed to help reduce destruction of transplanted islets and promote their successful implantation. These therapies may help transplant recipients achieve better function and durability of transplanted islets with fewer side effects. The ultimate goal is to achieve immune tolerance of the transplanted islets, where the patient's immune system no longer recognizes the islets as foreign. If achieved, immune tolerance would allow patients to maintain transplanted islets without long-term immunosuppression.
Researchers are also trying to find new approaches that will allow successful transplantation without the use of immunosuppressive drugs. For example, one study is testing the transplantation of islets that are encapsulated with a special coating designed to prevent rejection.
Shortage of Islets
A major obstacle to widespread use of islet transplantation is the shortage of islets. Although organs from about 7,000 deceased donors become available each year in the United States, fewer than half of the donated pancreases are suitable for whole organ pancreas transplantation or for harvesting of islets—enough for only a small percentage of those with type 1 diabetes. However, researchers are pursuing various approaches to solve this problem, such as transplanting islets from a single donated pancreas, from a portion of the pancreas of a living donor, or from pigs. Researchers have transplanted pig islets into other animals, including monkeys, by encapsulating the islets or by using drugs to prevent rejection. Another approach is creating islets from other types of cells, such as stem cells. New technologies could then be employed to grow islets in the laboratory.
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