Pancreatic Islet Transplantation - Article Pancreas
Article: Pancreatic Islet Transplantation
The pancreas, an organ about the size of a hand, is located behind the lower part of the stomach. It makes insulin and enzymes that help the body digest and use food. Spread all over the pancreas are clusters of cells called the islets of Langerhans. Islets are made up of two types of cells: alpha cells, which make glucagon, a hormone that raises the level of glucose (sugar) in the blood, and beta cells, which make insulin.
Insulin is a hormone that helps the body use glucose for energy. If your beta cells do not produce enough insulin, diabetes will develop. In type 1 diabetes, the insulin shortage is caused by an autoimmune process in which the body's immune system destroys the beta cells.
In an experimental procedure called islet transplantation, islets are taken from a donor pancreas and transferred into another person. Once implanted, the beta cells in these islets begin to make and release insulin. Researchers hope that islet transplantation will help people with type 1 diabetes live without daily injections of insulin.
Scientists have made many advances in islet transplantation in recent years. Since reporting their findings in the June 2000 issue of the New England Journal of Medicine, researchers at the University of Alberta in Edmonton, Canada, have continued to use a procedure called the Edmonton protocol to transplant pancreatic islets into people with type 1 diabetes. A multicenter clinical trial of the Edmonton protocol for islet transplantation is currently under way, and results will be announced in several years. According to the Immune Tolerance Network (ITN), as of June 2003, about 50 percent of the patients have remained insulin-free up to 1 year after receiving a transplant. A clinical trial of the Edmonton protocol is also being conducted by the ITN, funded by the National Institutes of Health and the Juvenile Diabetes Research Foundation International.
Researchers use specialized enzymes to remove islets from the pancreas of a deceased donor. Because the islets are fragile, transplantation occurs soon after they are removed.
During the transplant, the surgeon uses ultrasound to guide placement of a small plastic tube (catheter) through the upper abdomen and into the liver. The islets are then injected through the catheter into the liver. The patient will receive a local anesthetic. If a patient cannot tolerate local anesthesia, the surgeon may use general anesthesia and do the transplant through a small incision. Possible risks include bleeding or blood clots.
It takes time for the cells to attach to new blood vessels and begin releasing insulin. The doctor will order many tests to check blood glucose levels after the transplant, and insulin may be needed until control is achieved.
Transplantation: Benefits, Risks, and Obstacles
The goal of islet transplantation is to infuse enough islets to control the blood glucose level without insulin injections. For an average-size person (70 kg), a typical transplant requires about 1 million islets, extracted from two donor pancreases. Because good control of blood glucose can slow or prevent the progression of complications associated with diabetes, such as nerve or eye damage, a successful transplant may reduce the risk of these complications. But a transplant recipient will need to take immunosuppressive drugs that stop the immune system from rejecting the transplanted islets.
Researchers are trying to find new approaches that will allow successful transplantation without the use of immunosuppressive drugs, thus eliminating the side effects that may accompany their long-term use.
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. Immunosuppressive drugs are needed to keep the transplanted islets functioning.
The Edmonton protocol uses a combination of immunosuppressive drugs, also called antirejection drugs, including dacliximab (Zenapax), sirolimus (Rapamune), and tacrolimus (Prograf). Dacliximab 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.
These drugs have significant side effects and their long-term effects are still not known. Immediate side effects of immunosuppressive drugs may include mouth sores and gastrointestinal problems, such as stomach upset or diarrhea. Patients may also have increased blood cholesterol levels, decreased white blood cell counts, decreased kidney function, and increased susceptibility to bacterial and viral infections. Taking immunosuppressive drugs increases the risk of tumors and cancer as well.
Researchers do not fully know what long-term effects this procedure may have. Also, although the early results of the Edmonton protocol are very encouraging, more research is needed to answer questions about how long the islets will survive and how often the transplantation procedure will be successful.
A major obstacle to widespread use of islet transplantation will be the shortage of islet cells. The supply available from deceased donors will be enough for only a small percentage of those with type 1 diabetes. However, researchers are pursuing avenues for alternative sources, such as creating islet cells from other types of cells. New technologies could then be employed to grow islet cells in the laboratory.
For More Information
For information about clinical trials in islet transplantation, see
Source: National Institute of Diabetes and Digestive and Kidney Diseases
Cache Date: December 10, 2004