Introduction and Objective: Transplantation of free islets is limited by the need for systemic immune suppression. To protect transplanted cells from the autoimmune response and avoid the negative effects of systemic immune suppression, which can include damage to remaining and transplanted beta cells, we are developing physical immune-protective hydrogels. We demonstrated good survival and function in our proprietary synthetic hydrogels in vitro and in vivo and are moving towards a single, retrievable device with a high surface area (LifeRaftsTM).Methods: Fluorescently labelled proteins were used for size exclusions experiments. Blood glucose, C-peptide, and HbA1c of encapsulated donor islets were measured following implantation into streptozotocin (STZ)-induced diabetic immunocompetent rodents. LifeRaftsTM were printed using a commercially available bioprinter and either assessed for viability and protein secretion in vitro or implanted into healthy animals to assess graft survival and host-implant interactions.Results: Protein exclusion could be fine-tuned to excluded IgG, while maintaining good cell viability after encapsulation or printing. Encapsulated rat islets demonstrated rapid and sustained blood glucose control for 110+ days in immunocompetent mice and rats while the functionality of human islet could be extended in mice and large animals, as indicated by reduced blood glucose and increased C-peptide and HbA1c levels. Explanted LifeRaftsTM showed visible blood vessels early post-implant.Conclusion: Our proprietary, retrievable hydrogels showed strong immune protection for both allogenic and xenogeneic transplantation, without any immunosuppression. Early LifeRaftsTM demonstrated promising tissue integration. We are currently preparing for functional studies using LifeRaftsTM, in pursuit of a single retrievable device for functional cell therapy.
H. Stover: Employee; Allarta Life Science Inc.
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