Perspectives in Pancreatic and Islet Cell Transplantation for the Therapy of IDDM

Abstract

Endocrine pancreas transplantation could provide an ideal solution to the problem posed by IDDM. Although preliminary clinical success achieved over the past few years has been considerably higher with whole pancreatic transplant than with isolated islet grafts, both approaches remain experimental. Islet grafts might gain, over time, increasing credibility and might eventually provide an easier alternative in terms of grafting procedures and patient management, as compared with the more “traumatizing” whole-pancreas transplantation, but only if the pending technical problems are fully surmounted. Combined pancreas/kidney (either simultaneous pancreas/kidney [SPK] or pancreas after kidney [PAK]) transplantation, under general immunosuppression, in IDDM patients also suffering from end-stage renal disease (ESRD) is a procedure that may be worth pursuing in selected cases. However, there are still quite serious reservations about the scaled-up applicability of pancreas transplant alone (PTA) in patients with “brittle” IDDM; major restrictions are not only the necessity of pharmacological immunosuppression, but also the lower functional performance of PTA, especially as compared with SPK grafting. In terms of islets, as problems of human islet yield and purity are gradually being overcome, the problem of islet graft-directed immune destruction hampers the success of ongoing clinical trials in IDDM patients. The invariable requirement of general immunosuppression affects pancreatic as much as islet grafts, although a number of alternative, yet experimental, immunoprotection strategies in progress might suit islets better than they would whole organs. Another issue concerns the relative inadequacy of cadaveric donor organ availability, the requirements of which are more stringent for islets because of the persistent variability of islet cell yield per organ. Tremendous experimental efforts are in progress to create xenogeneic porcine/bovine islets and, perhaps over a longer period of time, human/nonhuman engineered insulin-producing cells suitable for graft within special immunoisolation barrier membranes.