Islet transplantation. The connection of experiment and clinic exemplified by the transplantation of islets of Langerhans.
Since approximately 25 years islet transplantation as a mean for the treatment of diabetes has been developed from early attempts in rodents to first clinical applications in man in recent years. The review describes the results obtained in diabetic rats including metabolic effects as well as prevention of late complications. In the syngeneic system (Lewis-rats) the intraportal transplantation of 1,000-2,000 isolated islets may cure streptozotocin-induced diabetes for the whole lifespan of the animal. In the allogeneic system (across a major histocompatibility barrier), however, isolated islets are highly immunogenic. According to present knowledge, mainly class-II antigen bearing cells are responsible while the role of the endocrine cells seems to be less important. By various in vitro methods (e.g. low temperature culture at 24 degrees C) it was possible to induce immunoalteration of allogeneic islets which was followed by long-term acceptance by the host in rodents. Whether the same technique is effective in larger animals and in man remains open. New technologies for the isolation of high numbers of pure islets from human pancreatic glands have been the key for the use of islet transplantation in man in several centers. The review describes the details regarding institutions as well as results in patients on the basis of the International Islet Transplant Registry which is located at Giessen University. Although longer lasting insulin independency (longest lasting effect 2 1/2 years) has been observed only in a few patients, islet transplantation has been proven to be a very safe procedure for the patient. It is hoped that with increasing experiences regarding the factors which at present limit the function as number and quality of islets, immunosuppressive protocols etc. islet transplantation will develop to a definite alternative to whole-organ transplantation. One of the most important challenges for modern medicine is the fact of a worldwide increase of diabetic long-term complications such as kidney failure, coronary and peripheral vascular disease, blindness and neuropathy. Although intensified insulin treatment in a small percentage of patients may moderate morbidity and mortality, from experimental work there is sufficient evidence suggesting that only the restoration of normoglycemia early in the course of the disease may prevent complications. This, however, can only be achieved by the replacement of the destroyed islets of Langerhans either by transplantation of an intact vascularised pancreas or by isolated islets.(ABSTRACT TRUNCATED AT 400 WORDS)
Federlin
K F
KF
Third Medical Dept., Justus-Liebig-University Giessen, Germany.
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D004285:Dogs; D049673:History, 20th Century; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000266:history; D051381:Rats; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous