Tannic acid-encapsulated islets delay immune rejection following transplantation

Abstract

Abstract Islet transplantation can restore β-cell function in patients with Type 1 diabetes (T1D), 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. (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. Allogeneic encapsulated B6 islets also restored euglycemia in diabetic NOD recipients 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, displaying a potential intervention to delay xenotransplant rejection. Our results support the hypothesis that (PVPON/TA) coatings are immunoprotective and may promote islet graft acceptance following transplantation.