Canine islet autografts with and without administration of cyclosporine

Cyclosporine administration prolongs the survival of immediately vascularized allografts. However, its role in the prevention of rejection of dispersed pancreatic islet allografts is uncertain, and some studies have suggested that it may be harmful. We performed total pancreatectomies in 21 mongrel dogs, followed by intrasplenic autotransplantation of islet-enriched, dispersed pancreatic tissue prepared by means of ductal perfusion and collagenase digestion. Ten dogs received no other therapy (controls) and 11 received orally administered cyclosporine from the day before to 30 days after transplantation. Therapeutic blood levels of cyclosporine were documented by means of high-pressure liquid chromatography. There was no difference in engraftment in six of 10 controls, and eight of 11 cyclosporine-treated dogs remained normoglycemic for more than 30 days. Intravenous glucose tolerance test results (K values), fasting serum insulin levels, and insulin secretion in response to a glucose challenge were similar in the two groups. There were two late treatment failures in the control group and one in the cyclosporine-treated group. We were unable to detect an adverse effect of cyclosporine on the engraftment or function of canine islet autografts. We conclude that cyclosporine remains a promising drug for use in studies of islet transplantation in human beings.