Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes

Summary: The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients. Transplantation of conformal-coated islets into a confined well-vascularized site allows long-term diabetes reversal in fully MHC-mismatched diabetic mice without immunosuppression. Here, we demonstrated that human SC islets reaggregated from cryopreserved cells display glucose-stimulated insulin secretion in vitro. Importantly, we showed that conformally coated SC islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. Overall, these results provide support for further evaluation of safety and efficacy of conformal-coated SC islets in larger species. : Scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Islet encapsulation may eliminate the need for chronic immunosuppression. Conformal coating seeks to overcome limitations of traditional microencapsulation. Transplantation of conformal-coated stem cell-derived islets might extend the applicability of islet transplantation to a larger cohort of patients. Keywords: encapsulation, β cells, polyethylene glycol, alginate, insulin, Type 1 Diabetes, islet transplantation, stem cell-derived islets, conformal coating, thiol-ene click chemistry