2026-10-14T07:25:17Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33369088 2026-09-29T14:19:31Z category_24454 portal_785 item_type_1 month_year_09_2026

<b>Microgels Containing Protease Resistant CXCL12 and FasL Enable Long Term Allo-Islet Function Without Systemic Immunosuppression</b> Fatma Dogan (1862101) Assia El Babsiri (24667559) Esin Ozkan (24667560) Sitong Ye (11242310) Katie Lu (10074808) Aaruni Arora (24667565) Kento Kawai (8268189) Ryo Otsuka (652067) Timothy A. Brauns (24667569) Patrick M. Reeves (24667572) Ann E. Sluder (24667575) Mark C. Poznansky (353701) Other biological sciences not elsewhere classified Islet Allograft Immunomodulation Type 1 Diabetes Islet Cell Transplantation CXCL12 Chemokine Protein Transplantation Immunology Mouse Model Allotransplantation <p dir="ltr">Type 1 diabetes (T1D) is a chronic disease characterized by the autoimmune destruction of insulin-producing beta cells in the pancreas. Replacement of beta cells by islet transplantation has proven to be successful in providing a functional cure for T1D. We have previously shown that microencapsulation of allo or xeno-islets with CXCL12 promotes beta cell function, provides immune protection, and facilitates vascularization at the graft site in both small and large animal models of T1D. In addition, streptavidin-Fas Ligand (SA-FasL) microgels have been shown to induce immune acceptance of allogeneic islets through expansion of T regulatory cells (Tregs) in combination with short-term systemic immune suppression. This study evaluated a combination of these two complementary approaches for extending allo-islet graft survival in a mouse model of T1D through the co-delivery of SA-CXCL12 or a protease-resistant variant of the chemokine (SA-prCXCL12) and SA-FasL within biotinylated microgels in an allogeneic transplant setting. We demonstrated that microgels coated with SA-FasL and SA-prCXCL12, when co-transplanted with allogeneic islets, sustained long-term (6 months) diabetes reversal in STZ-treated mice without any systemic immunosuppression more effectively than either agent alone. Our findings demonstrate in this murine model of diabetes that microgels delivering a combination of SA-prCXCL12 and SA-FasL induces long-term local immune protection of the allo-islet graft, enhances intragraft Treg recruitment and improves graft vascularization while abrogating the need for any systemic immune suppression.</p> 2026-09-29T14:19:31Z Image Figure 10.2337/figshare.33369088.v1 https://figshare.com/articles/figure/_b_Microgels_Containing_Protease_Resistant_CXCL12_and_FasL_Enable_Long_Term_Allo-Islet_Function_Without_Systemic_Immunosuppression_b_/33369088 CC BY-NC-SA 4.0