Revascularization and microcirculation of freely grafted islets of langerhans

A considerable number of experimental studies have demonstrated that tile r eestablishment of an appropriate microvascular supply is an essential prere quisite for successful pancreatic islet transplantation. Freely transplante d islets show the first signs of angiogenesis (i.e., capillary sprout forma tion and protrusion) as early as days after transplantation, and the entire vascularization process is completed after 10 to 14 days, Cryopreservation and culture of the isolated islets before transplantation and hyperglycemi a of tile transplant recipient seem not to affect the vascularization proce ss essentially. In addition, immunosuppressive drugs, such as cyclosporin a nd 15-deoxyspergualin, do not or only slightly inhibit revascularization of syngeneic islets: however, the are not able to prevent completely xenograf t-induced microvascular perfusion failure. In contrast, novel immunosuppres sants (e.g., RS-61443) or dietary supplementation of the antioxidant vitami n E were shown to prevent microvascular graft rejection almost completely, including leukocyte recruitment and capillary prl fusion failure. Thus the development of novel strategies to improve posttransplant islet function sh ould include concepts that accelerate the vascularization process and prote ct the newly formed microvasculature from rejection-mediated injury. The im provement of islet graft vascularization and the maintenance of adequate mi crovascular perfusion will contribute to the increased success of pancreati c islet transplantation.