89-OR: Immunoprivileged Hydrogels Extend Functionality of Islets in Immunocompetent Animals

Abstract

Background: Despite the promise of current islet cell transplantation, the need for systemic immune suppression significantly limits its utility for patients with diabetes. Until safe and immune-evasive cells are realized, physical immuno-protection offers an alternate route to allogeneic islet implants. Our proprietary synthetic hydrogels provide shape-agnostic, robust and retrievable Islet environments with anti-fouling and non-fibrotic properties. Methods: Rat and human donor islets were encapsulated and implanted in the peritoneal space of streptozotocin (STZ)-induced diabetic immunocompetent mice and pigs to assess islet functionality over time through measurement of blood glucose, C-peptide, and HbA1c. Next generation shape-agnostic hydrogels were also tested for in-vitro and in-vivo function. Results: Our hydrogels enabled rapid and persistent blood glucose control for 140+ days in immunocompetent mice with marginal loads of 1000 rat IEQ/mouse. Human donor islet function in mice was extended to day 45 (~8x longer than free human islets), with C-peptide detected at day 50, and corresponding HbA1c decreases. Our hydrogels showed minimal fibrosis when explanted after 45 days and showed robustness and integrity at day 340 post-implant in immunocompetent mice. Next-gen shape-agnostic hydrogels successfully excluded immune components including IgG and maintained good islet function in vitro. Our data also demonstrate function of human donor islets in immunocompetent pigs, based on C-peptide and cell viability data. Conclusion: Our proprietary synthetic and retrievable hydrogels show strong immune protection in xenogenic transplants of donor islets into immune-competent animals. We are currently scaling to therapeutic doses in large animals, in pursuit of a curative therapy based on an optimal balance of Islet protection and functionality, without immunosuppression. Disclosure H.Stover: Employee; Allarta Life Science Inc.