Oxygenation of islets and its role in transplantation.

OBJECTIVE

To summarize recent studies on the oxygenation of pancreatic islets and its role in islet transplantation.

RESULTS

Pancreatic islet cells are highly sensitive to hypoxic conditions. Hypoxia contributes to poor islet yield at isolation, as well as inflammatory events and cellular death during culture and early posttransplantation. Use of oxygen carriers, such as semifluorinated alkanes, during pancreas preservation and gas-permeable devices for islet culture and transport has in recent studies proven beneficial. Beta-cell death can be limited posttransplantation by targeting hypoxia-induced cellular pathways that cause apoptotic death. Owing to low revascularization, impaired oxygenation seems to prevail in intraportally transplanted islets. Means to improve revascularization, oxygenation and function of transplanted islets can be achieved not only by stimulating angiogenic factors, but also by decrease of angiostatic factors such as thrombospondin-1 in islets for transplantation. Moreover, bone-marrow-derived cells, such as mesenchymal stem cells and hematopoietic stem cells, can induce or contribute to increased revascularization.

CONCLUSIONS

Low oxygenation of islets contributes to cellular death and dysfunction during preparation of islets for transplantation, as well as posttransplantation. Interventions at these different steps to ensure adequate oxygenation have the potential to improve the results of clinical islet transplantation.