Effects of cyclosporine A on the process of vascularization of freely transplanted islets of Langerhans

Abstract

We studied in vivo the effect of cyclosporine A (CsA) on both pancreatic islet vascularization and microvascular perfusion using intravital fluorescence microscopy and the dorsal skinfold chamber model in Syrian golden hamsters. Syngeneic transplantation was performed in order to exclude allograft- or xenograft-induced microvascular alterations. To study the effect of CsA on islet angiogenesis and vascularization, animals received 20 mg/kg CsA daily from day 0 until day 14 after transplantation (group A). To study toxic effects of CsA on islet microcirculation, the grafts were allowed to vascularize without immunosuppression, and 20 mg/kg CsA was given daily from day 10 until day 20 after transplantation (group B). Quantitative analysis of the process of islet vascularization in group A revealed a functional capillary density (FCD) of 515.6±72.7 cm^–1 at day 6 after transplantation without further increase until day 14 (504.3±16.7 cm^–1). Islet transplants which were not treated with CsA during the process of angiogenesis/vascularization (group B) demonstrated a slightly but significantly (P<0.05) higher FCD (604.7±42.5 cm^–1) at day 14 after transplantation, indicating slightly improved vascularization when compared to transplants of group A. Additional CsA treatment of these islet grafts until day 20 did not induce derangements of microvascular perfusion (601.2±67.0 cm^–1), indicating that the immunosuppressive, drug has no toxic/detrimental effects on the transplants nutritional blood supply. We conclude that CsA only slightly alters the process of final vascularization of freely transplanted islets, and does not deteriorate nutritive perfusion of completely vascularized grafts.