*Purpose: Islet transplantation currently provides a cure for type 1 diabetes. Hepatic infusion of islets via the portal vein is clinically accepted in human, although this site has disadvantages including immediate blood-mediated inflammatory reaction, relative hypoxia, portal vein thrombosis, etc. To overcome these problems, we investigated if the pleural space is a suitable alternative as an islet transplantation site based on the high pO2 in the pleural space.

*Methods: Syngeneic and allogeneic murine islets were isolated and transplanted into streptozotocin induced diabetic B6 recipients. Islets were transplanted into intrapleural space and blood glucose concentration were monitored to check curing diabetes. Graft survival was defined as random fed blood glucose <250 mg/dl. Grafts were analyzed histologically up to 100 days post transplantation (Figure).

*Results: We demonstrated the reversal of hyperglycemia in diabetic mice after intrapleural injection of islets. Pathological observation showed vascularized, syngeneic islet grafts with normal insulin staining (Figure). We found that a minimum of two donors were required to cure diabetes in pleural space. Allogeneic islets rejected within 20 days (Figure) and early data suggest that the induction of systemic tolerance by an accepted kidney allograft prolonged the survival of these islets.

*Conclusions: We demonstrate that islets survive and function well in the pleural space in mice. The site is attractive for islet transplantation based on the oxygen rich environment and capacity for a large volume of cells. The site may be ideal for encapsulated syngeneic and allogeneic or stem cell derived islet products in which the transplanted volume is much greater. We are currently exploring the translational potential of the approach in a large animal model, which includes tolerance protocols.

« Back to 2020 American Transplant Congress