Islet Cell Transplantation

Definition
Purpose
Demographics
Description
Diagnosis/Preparation
Aftercare
Risks
Alternatives

Definition

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.

Purpose

Once transplanted, the new islet cells make and release insulin. Islet cell transplantation is primarily a treatment method for type 1 diabetes, but it can also be used to treat patients who have had their pancreas

KEY TERMS

Immunosuppression— A drug-induced state that prevents rejection of transplanted body parts.

Invasive— Used to describe a procedure that involves surgical cutting into the body.

Islet cell— The cell type within the pancreas that produces insulin.

Portal vein— The main vessel that carries blood to the liver.

Steroids— A component of commonly used immunosuppressive drugs that have negative effects on insulin production.

removed or damaged from other medical conditions or injuries.

Demographics

An estimated 120-140 million people worldwide suffer from type 1 diabetes and might possibly 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.

Description

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 machine to guide the placement of a small plastic tube, known as a catheter, through the upper abdomen and into the liver. The liver is used as the site for transplantation because the portal vein of liver is large and therefore, easier to access than smaller veins that supply the pancreas. In addition, 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. 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. 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 perfluor-ocarbon 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 relieving the extreme shortage of donor pancreases needed for the procedure.

Diagnosis/Preparation

To qualify as a candidate for islet cell transplantation, the patient must suffer from type 1 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 pancreas organs 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. Although 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 include 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.

Aftercare

Recovery time from the procedure itself is minimal. However, current technology requires that patients

WHO PERFORMS THIS 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.

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 that occurs, numerous blood glucose tests are performed, and injected insulin is used to keep blood glucose levels within normal ranges.

Risks

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 the procedure, the long-term success rate of these new protocols is not yet known. Graft death is a significant risk even years after a successful transplant. The longest reported successful graft using older protocols has been six years. Over time, the ability of grafts transplanted using new protocols and then sustained by the new immunosuppressive drug mixtures, will be determined.

The long-term use of immunosuppressive drugs by the patient poses an additional risk. There is relatively little experience and therefore, little data to date, pertaining to the long-term use of these drugs. It is difficult then, to predict what exact physical effects long-term immunosuppression may have. Some known side effects include high blood pressure, toxicity of the kidneys, and opportunistic infections.

Alternatives

One alternative to islet cell transplantation is transplantation of an entire pancreas, a much more invasive procedure. Whole organ transplant has historically had a better success rate than islet transplantation.

QUESTIONS TO ASK THE DOCTOR

• What are the chances that the procedure will allow me to no longer require insulin?
• If I do still require insulin after this procedure, will I be able to at least reduce the amount of insulin that I currently use?
• Will the immunosuppression before my procedure involve the use of steroids?
• What are my risks concerning long-term use of immunosuppressive drugs?

However, newer islet cell transplant protocols are approaching whole organ results, thus overcoming one of the most important differences between the two procedures.

Resources

BOOKS

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.

Shapiro, A., et al. Islet Transplantation and Beta Cell Replacement Therapy, 1st ed. London: Informa Healthcare, 2007.

PERIODICALS

“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.

ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 342-2383. http://www.diabetes.org.

Immune Tolerance Network (ITN). 5743 South Drexel Avenue, Suite 200, Chicago, IL 60637. (773) 834-5341. http://www.immunetolerance.org.

International Pancreas Transplant Registry (IPTR). University of Minnesota Department of Surgery, Mayo Mail Code 280, 420 Delaware Street SE, Minneapolis, MN 55455-0392. http://www.iptr.umn.edu/.

Michelle Johnson, MS, JD

Laura Jean Cataldo, RN, EdD

IV rehydration seeIntravenous rehydration