2427-P: Towards Clinical Application: Permanently Cross-Linked Hydrogels to Deliver Functional Islets

Introduction and Objective: The dangers of Type I diabetes stem from its potential to cause severe, long-term health complications affecting multiple organ systems. While islet transplantation is a viable clinical option, it remainsconstrained by limited donor availability and the requirement for lifelong immunosuppression. To overcome this challenge, we are developing synthetic hydrogels that physically protect transplanted cells from both allo and autoimmune attack, while allowing metabolic exchange. Allarta’s proprietary hydrogels have shown extended survival and function for primary rat as well as primary and stem cell-derived human islets, in vitro and in vivo. Building on these results, we are advancing toward a first-in-human clinical trial with donor islets. Methods: Islets derived from human donor pancreata, human pluripotent stem cells, and Wistar and Lewis rats were studied. Blood glucose and C-peptide of encapsulated islets were measured following implantation into streptozotocin (STZ)-induced diabetic immunocompromised and immunocompetent rodents. Viability and function were tested before implantation and after explantation. Further analyses included hydrogel diffusion limits and mechanical strength, and pericapsular overgrowth (PCO). Results: Protein exclusion could be fine-tuned to exclude IgG, while maintaining good cell viability and function after encapsulation. Encapsulated rat islets demonstrated rapid and sustained blood glucose control for weeks in mice and rats while the functionality of human donor and stem cell-derived islet could be extended in mice, as indicated by reduced blood glucose and increased C-peptide levels. Conclusion: Our proprietary, retrievable hydrogels showed strong immune protection for both allogenic and xenogeneic transplantation, without any immunosuppression. We are currently running CTA/FDA-enabling studies to prepare for a first-in-human clinical trial with donor-derived islets. Disclosure H. Stover: None. Funding JDRF (2-IND-2023-1449-I-X)