Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate
Xiaomeng Hu, Kathy White, Chi Young, Ari G. Olroyd, Paul Kievit, Andrew J. Connolly, T. Deuse, Sonja Schrepfer
Abstract
Allogeneic transplantation of pancreatic islets for patients with difficult-to-control diabetes mellitus is severely hampered by the requirement for continuous immunosuppression and its associated morbidity. We report that allogeneic transplantation of genetically engineered (B2M−/−, CIITA−/−, CD47+), primary, hypoimmune, pseudo-islets (p-islets) results in their engraftment into a fully immunocompetent, diabetic non-human primate wherein they provide stable endocrine function and enable insulin independence without inducing any detectable immune response in the absence of immunosuppression. Hypoimmune primary p-islets may provide a curative cell therapy for type 1 diabetes mellitus.