Replacement of pancreatic beta cells as treatment for diabetes mellitus: a review.
At the present time, two major factors limit further clinical application of islet cell transplantation in treatment of the insulin-deficient diabetic patient. First, the yield of islet tissue obtainable from a single donor pancreas is insufficient for adequate reconstitution of normal beta cell mass. The purification procedures required to eliminate acinar contamination and allow safe portal vein infusion cause large islet cell losses. Other procedures designed to minimize islet loss result in crude preparations containing substantial acinar tissue. In dogs and rats, crude preparations have been inoculated with safety into the spleen and function well in this location, but such a procedure might not be feasible in the human. Preliminary trials of these techniques in the monkey have not been successful. Second, dispersed and isolated islets inoculated into any site are exceptionally vulnerable to rejection and cease to function within a few days. Successful human islet allografting must await development of improved techniques of histocompatibility matching and/or immunosuppression. An additional question, unanswered in experiments to date, relates to the probable requirement for accuracy in replacement of alpha cells and beta cells for cure of the insulin-deficient juvenile diabetic patient. In rats, transplantation of large volumes of islet cells has resulted in hyperglucagonemia, hyperinsulinemia, and polyphagia, although the rats remain normoglycemic and have normal glucose tolerance tests. Bewick has elicited hyperinsulinemia in dogs by denervation and shunting the pancreatic venous drainage from portal to systemic. The metabolic effects of this abnormal state have not been adequately studied. These unresolved issues mandate that pancreatic transplantation remain an experimental procedure in humans. Whole or segmental pancreatic implants are technically feasible and are capable of function for extended periods of time. Islet implantation is reserved for carefully controlled experiments and in patients immunosuppressed for other organ transplants.
D000375:Aging; D000818:Animals; D046508:Culture Techniques; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D003925:Diabetic Angiopathies / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy; D016381:Islets of Langerhans Transplantation; D009926:Organ Preservation; D016035:Pancreas Transplantation; D014181:Transplantation Immunology; D014184:Transplantation, Homologous