Islet transplantation in Type-I diabetes: current state and prospects

Abstract

Islet transplantation in Type I diabetes mellitus is appealing because of its potential for curing the disease, its relative simplicity and the potential for immunomodification of the graft so that immunosuppression may be avoided. Transplantation of isolated islets is widely used in experimental animals but has had little impact clinically. In contrast, vascularised pancreas grafts in patients are increasingly successful and this success will inevitably result in an even greater shortage of donor organs for islet isolation. Islet grafts can cure diabetes in animal models and prevent the development of diabetic complications, and in some situations even allografts can be accepted and function without immunosuppression. In contrast, vascularised grafts require a major operative procedure and continuing immunosuppression. Recurrence of autoimmune disease in the grafted islets may also be a problem. The shortage of donor tissue may be overcome by the use of xenogeneic islets, perhaps from the pig pancreas. The induction of immunological tolerance has been reported for pig islet xenografts in mice, and xenogeneic islets also appear to be relatively resistant to disease recurrence in a murine model of spontaneous autoimmune diabetes. Thus, vascularised pancreas allografts may be most suitable for and perhaps be restricted to patients who also need a renal transplant and immunosuppression for this, while isolated islet grafts of perhaps xenogeneic origin may become a more suitable treatment for patients early in the course of their disease if adequate immunosuppressive protocols, ideally resulting in immunological tolerance, can be developed.