Critical islet mass for successful porcine islet autotransplantation

A major reason for the failure of clinical islet transplantations maybe a l imited islet mass. The aim of this study was to determine the critical isle t mass necessary for normalization of glucose metabolism in a porcine model . Diabetes was induced by total pancreatectomy. The splenic lobe of the pan creas was intraductally distended with UW-solution containing 2.67-3.33 mg/ ml collagenase, and the distended pancreas was digested in a continuous dig estion filtration device. The islets were purified on a isoosmotic Ficoll-s odium-diatrizoate gradient. The survival, period of the diabetic recipients in group 2 and 3 receiving, respectively, a low (2.14+/-0.39 mu L/kg body weight) and a high (4.99+/-0.83 mu L/kg body weight) islet mass was signifi cantly prolonged compared to that of diabetic recipients in group 1 receivi ng, no islet transplantation. However, the survival period of the recipient s in group 2 was not significantly different to that in group 3. Three reci pients of an islet mass of >5 mu l/kg body weight became normoglycemic (fas ting blood glucose <100 mg/dl) for more than two months. Furthermore, the g lucose and insulin release reactions to the glucose challenge were comparab le to that before pancreatectomy. Contrarily, an other five diabetic recipi ents of an islet mass of <4 mu L/kg body weight became a fasting blood gluc ose level of <200 mg/dl. The glucose and insulin release reactions to the g lucose challenge were improved only, but not normalized compared to that be fore pancreatectomy. The data presented in this study demonstrate that meta bolic normalization in pancreatectomized diabetic minipigs can be establish ed by autotransplantation of an islet mass of >5 mu l/kg body weight.