Clinical islet transplantation at the University of Alberta--the Edmonton experience

Abstract

While the field of islet transplantation has evolved over the past 30 years and exponential progress and increase in clinical activity has occurred during the past 5 years, it is clear that major challenges still remain, particularly in understanding why islet function seems to decay over time. High one-year rates of insulin independence, and high 5-year rates of partial islet function (with C-peptide secretion and protection from hypoglycemia) are now routine. Improved control of glycated HbA1c and reduced risk of recurrent hypoglycemia are benefits of islet transplantation irrespective of the status of insulin independence. If complete and sustained freedom from insulin is the primary objective, it is clear that whole pancreas transplantation still offers far superior metabolic reserve. However, the less interventional nature of islet infusion and avoidance of major surgery are advantages of islet transplantation over whole pancreas strategies. While the anti-rejection drugs available today may have had an acceptable safety profile in most islet transplant recipients, the drug-related and dose-limiting side effects have proved to be a challenge in some patients. Current islet-alone transplantation requires lifelong immunosuppression and is limited to patients with recurrent severe hypoglycemia and severe labile diabetes. More effective treatments are needed to control both acute rejection and recurrent autoimmunity. Remarkable opportunities lie ahead for improved islet survival, better engraftment and the possibility of expansion of islet mass both in culture and possibly within the patient after transplantation. Living-donor islet transplantation offers one option to expand the available donor supply, but remains controversial because of the potential for diabetes induction or other morbidities in a healthy donor. The development of less toxic immunosuppression and perhaps immunological tolerance will one day also have a huge impact on this field. Alternative tissue sources from either xenogenic sources or stem cells will ultimately solve the challenge of limited donor supply.