Type 1 diabetes (T1D) is an autoimmune disease of pancreatic β-cell death caused by islet-infiltrating leukocytes. Islet transplantation can restore β-cell function, however, limited islet availability, toxicity of immunosuppressants, and poor graft survival are major hurdles for clinical application. We hypothesize that islet encapsulation with a nanothin multilayer coating consisting of tannic acid (TA), an immunomodulatory antioxidant, and poly(N-vinylpyrrolidone) (PVPON), will provide an immunoprotective barrier and maintain β-cell function after transplantation. In support of our hypothesis, we demonstrate that (PVPON/TA)-encapsulated syngeneic NOD.Rag islets restored euglycemia after transplantation under the kidney capsule of streptozotocin-treated diabetic NOD mice by more than 30 days in comparison to non-encapsulated islets. Encapsulated allogeneic B6 islets also restored euglycemia in diabetic NOD mice and delayed rejection by 7.5 days in contrast to non-encapsulated islets. Gene expression of allogeneic B6 islets at 5 days post-transplant displayed an increase in Ins2 (6-fold), Gcg (6-fold), Pdx1 (5-fold), Ccl22 (3-fold), and Arg1 (2.5-fold) mRNA accumulation with (PVPON/TA)-encapsulated islet grafts, suggesting a potential shift toward an alternatively-activated M2 macrophage phenotype. To address limited islet availability, the use of (PVPON/TA)-encapsulated differentiated neonatal porcine islets restored euglycemia and maintained β-cell function for more than 200 days after transplantation into diabetic NOD.scid mice. Our results support the hypothesis that islet encapsulation with (PVPON/TA) coatings maintain function and may elicit protection following islet allo- and xenotransplantation. Future studies will determine the immunological mechanism of protection following (PVPON/TA)-encapsulation of islets.


J. Barra: None. H.M. Tse: None.

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