Transplantation of islets of langerhans.

The inadequacy of the present management of diabetes mellitus is reflected in the high morbidity and mortality caused by the long-term complications of the disease. Present evidence suggests that this is due to the inability to achieve strict diabetic control. This could possibly be attained by the successful transplantation of isolated islets of Langerhans. Rejection is the major cause of graft failure after transplantation. The susceptibility of isolated islet allografts to rejection was assessed in non-immunosuppressed and immunosuppressed rats, and their survival compared with that of other allografts. Streptozotocin-induced diabetic rats received in excess of 500 islets from six adult donors. The pancreases were excised, digested with collagenase and after separation from the unwanted exocrine tissue, on a Ficoll gradient, the isolated islets were transplanted intraportally. Functional viability was confirmed by in vitro and in vivo tests. The median survival of islet allografts in untreated recipients was significantly shorter than the median survival of kidney, heart and skin allografts transplanted across the same immunological barrier. Recipient immunosuppression with azathioprine, azathioprine and prednisolone, antilymphocyte serum or cyclophosphamide did not improve islet allograft survival. Macrophage suppression, using silica, resulted in the indefinite survival of seven out of sixteen allografts. Specific immunosuppression was more effective in prolonging islet allograft survival but not as effective as that for organ allografts. Passive enhancement resulted in the indefinite survival of four out of ten allografts. Graft survival was not improved by using serum from rats bearing a functioning, enhanced, islet allograft or by transplanting islets into rats bearing a functioning, enhanced, donor strain heart allograft. It was concluded that isolated islet allografts are more susceptible to rejection than organ allografts and that present immunosuppression is less effective in abrogating their rejection. The present state of human islet transplantation was reviewed.