Better vascular engraftment and function in pancreatic islets transplanted without prior culture

Aims/hypothesis: Recent studies suggest that donor endothelial cells may contribute to islet graft revascularisation. Since islet endothelial cells disappear during culture, we hypothesised that transplantation of islets without prior culture is beneficial for their engraftment. Methods: Cultured (4-7 days) or freshly isolated islets (< 4 h after donor pancreas extirpation) were syngeneically transplanted into Wistar-Furth rats and C57Bl/6 mice beneath the renal capsule. Islet graft revascularisation was evaluated by measuring vascular density, blood flow and tissue oxygen tension. Islet graft function was investigated by a minimal islet mass model in inbred mice (C57Bl/6). Results: Four days after implantation, the partial pressure of oxygen (pO(2)) in the transplanted cultured islets was less than 10 mmHg (1.33 kPa), but tended to be higher in grafts composed of freshly isolated islets. The pO(2) in the grafts of freshly isolated islets had more than doubled 4 weeks later, whereas the pO(2) in the grafts of cultured islets remained at values similar to those recorded 4 days after transplantation. Transplanted freshly isolated islets also had a higher vascular density than transplanted cultured islets (similar to 40 vs similar to 25% of that in endogenous islets) when investigated 1 month post-implantation. When applying a minimal islet mass model in inbred mice, 200 freshly isolated islets cured alloxan-diabetic mice in all cases, whereas only 33% of the group receiving similar numbers of cultured islets were cured. Conclusions/interpretation: Transplantation of pancreatic islets without prior culture is beneficial for their vascular engraftment and function.