Long term Glycemic Control Using Polymer Encapsulated, Human Stem-Cell Derived β-cells in Immune Competent mice

Abstract

The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in diabetic patients ¹ . Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically ² , but are limited by the adverse effects of lifetime immunosuppression and the limited supply of donor tissue ³ . The latter concern may be addressed by recently described glucose responsive mature β-cells derived from human embryonic stem cells; called SC-β, these cells may represent an unlimited human cell source for pancreas replacement therapy ⁴ . Strategies to address the immunosuppression concern include immunoisolation of insulin-producing cells with porous biomaterials that function as an immune barrier ^{5, 6} . However, clinical implementation has been challenging due to host immune responses to implant materials ⁷ . Here, we report the first long term glycemic correction of a diabetic, immune-competent animal model with human SC-β cells. SC-β cells were encapsulated with alginate-derivatives capable of mitigating foreign body responses in vivo, and implanted into the intraperitoneal (IP) space of streptozotocin-treated (STZ) C57BL/6J mice. These implants induced glycemic correction until removal at 174 days without any immunosuppression. Human C-peptide concentrations and in vivo glucose responsiveness demonstrate therapeutically relevant glycemic control. Implants retrieved after 174 days contained viable insulin-producing cells.