Islet Cell Transplantation
Pancreatic islet cell transplantation involves taking the cells that produce insulin from a second source such as a donor pancreas and transplanting them into a patient.
Once transplanted, the new islet cells make and release insulin. Islet cell transplantation is primarily a treatment method for type 1 (juvenile) diabetes, but it can also be used to treat patients who have had their pancreas removed or damaged from other medical conditions or injuries.
An estimated 120–140 million people worldwide suffer from type 1 diabetes and could benefit from this procedure. However, islet cell transplantation remains highly experimental at this time and occurs only as part of a clinical trial. The latest available data from the International Islet Transplant Registry indicate that, as of December 2000, about 500 procedures had been performed.
The transplantation procedure is very straightforward, relatively noninvasive, and takes less than an hour to complete. After the patient is given light sedation, the surgeon begins by using an ultrasound to guide the placement of a small plastic tube, known as a catheter, through the upper abdomen into the liver. The liver is used as the site for transplantation because the portal vein of liver is larger and easier to access than the veins that supply the pancreas, also, it is known that islet cells that grow in the liver closely mimic normal insulin secretion.
Once the catheter is in place, the surgeon takes the cells that have been extracted from the donor pancreas and infuses them into the liver. Extraction is done as close as possible to the time of transplantation because of the fragility of the islet cells. The extraction process uses specialized enzymes to isolate the islet cells from the other cell types found in the pancreas. Only 1–2% of the pancreas is made up of islet cells, an average of two pancreases are needed for one successful transplant.
Recent study has shown that the use of perfluorocarbon in the solution that preserves the pancreas before transplant allows older organs to be used as islet cell donors. New techniques have also been developed that allow the organs to be transported before being used for transplantation. These developments are initial steps to
During the infusion process, the cells travel through the portal vein and become lodged in the capillaries of the liver, where they remain to produce insulin as they normally would in the pancreas.
To qualify as a candidate for islet cell transplantation, the patient must suffer from type 1 (juvenile) diabetes and current insulin treatment methods must be insufficient. For example, some participants suffer from hypoglycemic unawareness, a condition where low blood sugar will cause very dangerous, unpredictable blackouts that cannot be controlled with insulin injections. The potential patient must also undergo extensive medical and psychological tests to determine their physical and mental appropriateness for enrollment in the trial. If the results of these tests support the candidacy, then sufficient donor pancreas tissue in the patient's blood type must be located. The patient is placed on an organ donor list. Waiting for more than a year is common.
In response to this long wait, research is ongoing to provide alternative sources of donor islet cells such as animal cells, a process known as a xenograft. Pigs are a particularly advantageous source of islet cells because human and pig insulin proteins differ by only one amino acid, and there is an extensive amount of fresh pancreases available from the pork industry. Other potential sources of donor islets cells include embryonic stem cells and cell lines of islet beta cells.
Prior to the transplantation, the patient must undergo a drug regime that suppresses the immune system so that the new cells will be accepted. Even though only cells are being transplanted, the amount of immunosuppression is the same as that required for a whole organ transplant. Current protocols for islet transplantation use a mixture of non-steroidal drugs, as those that include steroids have been shown to aggravate the diabetic condition of the patient and inhibit the insulin-producing function of the transplanted cells.
Future research in this area may include the use of monoclonal antibody therapy to induce tolerance in patients prior to transplantation.
Recovery time from the procedure itself is minimal. However, current technology requires that patients continuously remain on immunosuppressive drugs to avoid rejection of the new islet cells. Side effects from these drugs can increase the amount of time that the patient must remain hospitalized.
It takes some time for the cells to attach to the liver blood vessels and begin producing insulin. Until then, numerous blood glucose tests are performed, and injected insulin is used to keep blood glucose levels within normal ranges.
Until recently, success rates for this procedure were not promising. With success being defined as not requiring insulin for a full year after transplantation, the success rate from 1998–2000 was only about 14% of patients transplanted. However, newer procedures have been achieving at least short-term success rates approaching 80–100%, making the possibility of widespread use of this procedure much more feasible in the near future.
Because of the newness of these procedures, the long-term success rate of these new protocols is not yet known. Graft death is significant risk even years after a successful transplant. The longest reported successful graft using the older protocols was six years. As time goes on, the ability of the graft transplanted using the new protocols and sustained by the new immunosuppressive drug mixtures will be determined.
A third important risk is the long-term use of immunosuppressive drugs by the patient. There is relatively little experience with the long-term use of these drugs, so it is difficult to predict what the exact physical effects long-term immunosuppression may have. Some of the known side effects include high blood pressure, toxicity of the kidneys, and opportunistic infections.
One alternative to islet cell transplantation is a transplant with a whole pancreas, a much more invasive procedure. Whole organ transplant has historically had a better success rate than islet transplantation. However,
Farney, Alan C., and David E. R. Sutherland. "Pancrease and Islet Transplantation." In The Pancreas: Biology, Pathobiology, and Disease, edited by Vay Liang W. Go, et al. New York: Raven Press, 1993.
Robertson, R. Paul. "Pancreas and Islet Transplantation." In Endocrinology, edited by Leslie J. DeGroot, et al. Philadelphia: W.B. Saunders Company, 2001.
"Islet Cell Transplantation for Diabetes Turns Corner." Science Daily Magazine (August 28, 2002).
Perry, Patrick. "Zeroing in on a Cure for Diabetes." The Saturday Evening Post (January/February 2002): 38–43.
American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 342-2383. <www.diabetes.org>.
Immune Tolerance Network (ITN). 5743 South Drexel Avenue, Suite 200, Chicago, IL 60637. (773) 834-5341. <www.immunetolerance.org>.
Michelle Johnson, MS, JD
WHO PERFORMS THE PROCEDURE AND WHERE IS IT PERFORMED?
A specialist in transplantation would perform this procedure, and it would be done in a specialized center for diabetic research. Currently, about 15 centers around the world are performing this procedure.
QUESTIONS TO ASK THE DOCTOR
- What are the chances that the procedure will allow me to no longer require insulin or is being able to reduce the amount that I use a more realistic outcome?
- Will the immunosuppression before my procedure involve the use of steroids?
- What are my risks concerning long-term use of immunosuppressive drugs?