Self-Assembling Zwitterionic Nanogels As Immune Isolating Coatings for Stem Cell Derived Pancreatic Islet Transplantation

The concept of pancreatic islet transplantation to patients with diabetes to restore normoglycemia is a viable clinical strategy.  However, widespread clinical application of islet transplantation remains limited because of the harmful side effects of the necessary immunosuppressive therapy  to prevent host rejection of transplanted cells. Here we report the fabrication of a superbiocompatible nanogel and a novel coating strategy for protection of stem cell derived pancreatic islets against host rejection in vivo. Zwitterionic nanogels (100-300nm in size) were fabricated using an inverse emulsion polymerization synthesis scheme and further surface modified with CLICK reactive functional groups. Stem cell derived pancreatic islet cells were engineered to express azide functionalities on their cell membranes. Confocal fluorescence microscopy was used to verify covalent reaction and assembly of dual-layered nanogel coatings on engineered islet cell clusters. Cytocompatibility of coating and islet cell functionality were examined using a combination of in vitro glucose tolerance tests, live/dead staining, and in vivo studies on mice treated with streptozocin, a small molecule drug that destroys the beta cells. Our results indicate that the developed nanogel formulation and encapsulation strategy provides a viable strategy for prolonged protection and isolation of transplanted islets against host rejection