Immunocytochemical study of pancreatic islet revascularization in islet isograft : effect of hyperglycemia of the recipient and of in vitro culture of islets

We studied the revascularization process of isogeneic islets grafted into the kidney subcapsular space of streptozotocin-induced diabetic and nondiabetic rats by a double-labeling, indirect immunofluorescence technique using a rabbit antiserum to human factor VIII-related antigen (which identifies endothelial cells) and a guinea pig anti-insulin antiserum (which labels pancreatic beta cells). Freshly isolated islets contained a network of capillary endothelial cells, whereas 1-week-cultured islets at 37 degrees C have completely lost their intra-islet endothelial cells. Overnight cultured islets contained only occasional endothelial cells. When these islets were grafted under the kidney capsule of nondiabetic rats, they rapidly acquired a new endothelial cell lining as demonstrated by the positivity of staining for factor VIII-related antigen at day 5 after implantation. On the other hand, 1-week-cultured islets failed to become fully revascularized until day 7 after transplantation. Streptozotocin-induced diabetic rats grafted with 1000 islets normalized their blood glucose values (< 11 mM/L) 2-4 weeks after implantation, whereas transplantation of 2500-3000 islets resulted in normoglycemia after 4.7 +/- 2 days (mean +/- SD). Nevertheless, hyperglycemia of the recipient did not adversely affect the process of revascularization of islet isografts which initiated at day 3 and was almost completed by day 5 after implantation.