Microgels Containing Protease Resistant CXCL12 and FasL Enable Long-term Allo-Islet Function Without Systemic Immunosuppression.

Cotransplantation of allogeneic islets with microgels coated with streptavidin fused with Fas ligand and protease-resistant CXCL12 results in robust and sustained diabetes reversal for over 6 months in streptozotocin-induced diabetic mice and induces local immunomodulation, enhances Treg recruitment within the graft, and improves graft vascularization. This study addresses a critical challenge in cell transplantation, namely the need to develop technologies that enable local immunoprotection of the graft while eliminating the need for systemic immunosuppression. This combination microgel technology could offer a more favorable risk-benefit profile by reducing infection risks, organ toxicity, and tumorgenicity associated with the use of systemic immunosuppression. This novel combinatory immune modulatory approach is feasible and achieves anatomic site-specific immune protection while supporting long-term islet graft function without systemic immune suppression.