Introduction & Objective: The application of current islet cell transplantation is limited by the need for systemic immune suppression. Physically immuno-protective hydrogels offer a route to allogenic islet transplants. To assess the functionality of islets encapsulated in our proprietary synthetic hydrogels, we assessed in hydrogel robustness and islet function both in vitro and in immunocompetent diabetic animals, without any immunosuppression.
Methods: Rat and human donor islets were encapsulated in next generation shape-agnostic hydrogels and implanted in the peritoneal space of streptozotocin (STZ)-induced diabetic immunocompetent mice and rats to assess islet functionality over time through measurement of blood glucose, C-peptide, and HbA1c. The effect of islet loading and islet density was assessed in vitro and in vivo.
Results: Hydrogels successfully excluded IgG, maintained good islet function in vitro and showed visible blood vessels early post-implant. Encapsulated rat islets demonstrated rapid and sustained blood glucose control for 140+ days in immunocompetent mice and for 110+ days in immunocompetent rats. Our hydrogels also extended human donor islet function in mice, Yorkshire pigs and Gottingen minipigs, as indicated by reduced blood glucose and increased C-peptide and HbA1c levels. We noticed a dose-dependent effect on in vivo function, despite similar in vitro GSIS indices. When explanted from mice, rats or pigs, the encapsulated islets had indicators of good function and viability; and our hydrogels had no-to-minimal tissue response, as well as good robustness and integrity.
Conclusion: Our proprietary, retrievable hydrogels showed strong immune protection for both allogenic and xenogeneic transplantation, without any immunosuppression. 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.
H. Stover: None.
JDRF (2-IND-2023-1449-I-X)
