SUCCESSFUL ISLET AUTOTRANSPLANTATION AND ALLOTRANSPLANTATION IN DIABETIC PIGS

Background, Because of its anatomical and physiological similarities t o humans, the pig appears to be a suitable large animal model for prec linical studies of islet transplantation. The aim of this study was to investigate islet auto- and allotransplantation in a pig model with d iabetes induced by total pancreatectomy. Methods. Porcine islets were isolated by a continuous digestion-filtration device at 32 degrees C a nd purified by a discontinuous iso-osmolar Ficoll-sodium-diatrizoate g radient on a Cobe 2991. The purified islets were autografted into the Liver or the renal subcapsular space. The liver appears to be a more s uitable site for the islet grafts than the renal subcapsular space, an d the minimal amount of islets for reversal of diabetes is >5 mu l/kg of body weight, Results. Persistent normoglycemia (fasting blood gluco se level: 72.4+/-44.38 mg/dl) with a normal insulin secretion response to glucose stimulation was successfully achieved in five of six diabe tic pigs by implanting a sufficient islet mass into the Liver. Triple- drug immunosuppressive therapy with cyclosporine, azathioprine, and pr ednisolone did not prevent porcine islet allografts from experiencing early failure. However, the addition of 15-deoxyspergualin to the trip le-drug immunosuppressive regimen significantly prolonged the function of the islet allografts. When antithymocyte globulin was added to the above-mentioned immunosuppressive drug regimen, the normoglycemic per iod was prolonged to more than 1 month (fasting blood glucose level: 7 5.4+/-17 mg/dl). Conclusion. We conclude that autotransplantation with a sufficient islet mass can induce normoglycemia with a normal insuli n secretion response to glucose stimulation in pancreatectomized diabe tic pigs and that allotransplantation can be successfully achieved whe n 15-deoxyspergualin and antithymocyte globulin are combined with the triple-drug immunosuppression described above. However, this immunosup pressive protocol results in a. high rate of infectious complications.