Pancreatic islet transplantation

Abstract

Successful transplantation of the endocrine pancreas in Type I diabetes with complete correction of the glucose metabolic abnormalities may prevent progression or development of the microangiopathic complications of the disease. This could be achieved by transplantation of the whole pancreas as a vascularized graft (the only available clinical approach at present), transplantation of isolated islets or of fetal pancreas. Since transplantation of the pancreas as a vascularized graft is associated with a significant peri-operative morbidity and requires immunosuppression to prevent rejection it is unlikely to be applicable at a relatively early stage of the disease, before microangiopathic complications become irreversible. For this reason transplantation of pancreatic islets or fetal pancreas is the only approach likely to be acceptable. Transplantation of isolated islets in the rodent does correct experimental diabetes, but recurrence of disease is seen in the spontaneous diabetes of the Biobreeding (BB) rat and the non-obese diabetic (NOD) mouse. Furthermore suppression of rejection of allogenic islets has proved difficult. In large mammals, including man, the lack of a technique to prepare isolated islets in a relatively pure form has been a further obstacle to development. Recently this problem has been overcome, allowing separation of islets in relatively large numbers with adequate purity, bringing closer the time when clinical trials might be considered. However, rejection and disease recurrence are likely to remain major obstacles, although experimental work suggests that both can be overcome.