IMMUNOCYTOCHEMICAL STUDY OF PANCREATIC-ISLET REVASCULARIZATION IN ISLET ISOGRAFT - EFFECT OF HYPERGLYCEMIA OF THE RECIPIENT AND OF IN-VITROCULTURE OF ISLETS

We studied the revascularization process of isogeneic islets grafted i nto the kidney subcapsular space of streptozotocin-induced diabetic an d nondiabetic rats by a double-labeling, indirect immunofluorescence t echnique using a rabbit antiserum to human factor VIII-pelated antigen (which identifies endothelial cells) and a guinea pig anti-insulin an tiserum (which labels pancreatic beta cells), Freshly isolated islets contained a network of capillary endothelial cells, whereas 1-week-cul tured islets at 37 degrees C have completely lost their intra-islet en dothelial cells. Overnight cultured islets contained only occasional e ndothelial cells, When these islets were grafted under the kidney caps ule of nondiabetic rats, they rapidly acquired a new endothelial cell lining as demonstrated by the positivity of staining for factor VIII-r elated antigen at day 5 after implantation. On the other hand, 1-week- cultured islets failed to become fully revascularized until day 7 afte r transplantation. Streptozotocin-induced diabetic rats grafted with 1 000 islets normalized their blood glucose values (< 11 mM/L) 2-4 weeks after implantation, whereas transplantation of 2500-3000 islets resul ted in normoglycemia after 4.7+/-2 days (mean+/-SD). Nevertheless, hyp erglycemia of the recipient did not adversely affect the process of re vascularization of islet isografts which initiated at day 3 and was al most completed by day 5 after implantation.