Beta-cell replacement.

Abstract

heralded as the ideal therapy for the treatment of patients with insulin-dependent diabetes mellitus (IDDM) since it is a relatively safe procedure which should obviate the need for exogenous insulin therapy. More importantly, the resultant euglycaemia should prevent, and possibly even reverse, the devastating secondary complications of the disease. The Diabetes Control and Complications Trial demonstrated that the optimal control of blood glucose possible with intensive insulin treatment was associated with a reduced risk of developing diabetes related complications (nephropathy, retinopathy, accelerated coronary artery disease, and neuropathy) [1]. However, this aggressive insulin therapy substantially increased the frequency of dangerous hypoglycaemic episodes. Maintenance of tight glucose control over an extended period also required extraordinary patient effort. In contrast, islet transplantation can potentially provide better glucose control than even the best insulin therapy and should do so without the risk of severe hypoglycaemic events. Over 25 years have passed since the initial demonstration that islet transplantation could completely reverse diabetes in rodents [2]. These early reports provoked considerable interest in patients with the disease and their physicians. Since that time, the once formidable technical and immunologic problems have been solved and long term success of islet allotransplantation in rodents can be achieved using standard immunosuppression or by treating islets prior to transplantation. Unfortunately, the results in humans have been poor – almost all islet transplants in IDDM patients have failed. For islet transplantation to become a predictable, successful, and widespread treatment for IDDM, solutions must be found to overcome the need for continuous immunosuppression and for increasing the availability of insulin-producing tissue. The goal of this work group was to: 1) outline the major recent advances in transplantation and promising future directions in the field; 2) review the current status of clinical islet transplantation; 3) discuss strategies for preventing alloimmune and autoimmune destruction of transplanted islets; and 4) evaluate the scientific basis of using xenogeneic pancreatic islets and review the recent regulatory issues that surround the use of xenografts.