Fibrin supports subcutaneous neonatal porcine islet transplantation without the need for pre-vascularization.

Abstract

Neonatal porcine islets (NPIs) are a promising tissue source for clinical islet xenotransplantation. To facilitate graft monitoring and recovery if needed, an extra-hepatic transplant site would be optimal. In addition, islet transplantation into the portal vein has been associated with life-threatening intraperitoneal bleeding, portal vein thrombosis, hepatic steatosis, and loss of islet graft function. Although it is hypoxic, the subcutaneous space is a potential extra-hepatic location for clinical islet transplantation. In this study, we explore the benefits of fibrin scaffolds in enhancing the engraftment and long-term function of NPI grafts in this ectopic site. Diabetic immune-compromised mice were transplanted with 5000 NPIs under the kidney capsule (KC), and subcutaneously with or without fibrin (SC+F, SC, respectively). All mice were monitored for reversal of hyperglycemia and long-term metabolic function. All mice transplanted with NPI under the KC or SC+F (12/12 and 17/17, respectively) achieved normal fasting blood glucose levels between 5 and 22weeks post-transplantation and displayed normal glucose tolerance during an intraperitoneal glucose tolerance test. In contrast, NPIs transplanted SC with no fibrin (n=7) failed to obtain normoglycemia. Fibrin matrix facilitates engraftment of NPIs in the subcutaneous site of diabetic mice. These data support further investigation of the subcutaneous site for clinical islet xenotransplantation.