Islet transplantation in the subcutaneous space achieves long-term euglycaemia in preclinical models of type 1 diabetes.

Abstract

The intrahepatic milieu is inhospitable to intraportal islet allografts1–3, limiting their applicability for the treatment of Type 1 Diabetes (T1D). Although the subcutaneous space represents an alternate, safe and easily accessible site for pancreatic islet transplantation, lack of neovascularization and the resulting hypoxic cell death have largely limited the longevity of graft survival and function, and pose a barrier for the widespread adoption of islet transplantation in the clinic. Here we report the successful subcutaneous transplantation of pancreatic islets admixed with a device-free Islet Viability Matrix (IVM), resulting in long-term euglycemia in diverse immune-competent and immuno-incompetent animal models. We validate sustained normoglycemia afforded by our transplantation methodology using murine, porcine and human pancreatic islets, and also demonstrate its efficacy in a nonhuman primate model of syngeneic islet transplantation. Transplantation of the islet–IVM mixture in the subcutaneous space represents a simple, safe and reproducible method, paving the way for a new therapeutic paradigm for T1D.