Tannic Acid Capsules Decrease Redox-dependent Pro-inflammatory Responses to Prolong Islet Graft Survival After Transplantation

Type 1 Diabetes (T1D) is a chronic pro-inflammatory autoimmune disease consisting of islet-infiltrating leukocytes that produce free radicals to elicit pancreatic β-cell destruction. One promising treatment for T1D is islet transplantation; however, its clinical application is constrained due to limited islet availability, adverse effects of immunosuppressants, and declining graft survival. Islet encapsulation may provide an immunoprotective barrier to prevent immune-mediated rejection and maintain pancreatic β-cell function following transplantation. Using a novel cytoprotective nanothin multilayer coating consisting of tannic acid (TA), an immunomodulatory antioxidant, and poly(N-vinylpyrrolidone) (PVPON), we hypothesized that (PVPON/TA)-encapsulated islets can restore euglycemia in diabetic mice and provide an immunoprotective barrier that would prolong graft function post-transplant. We found that encapsulation of purified islets was efficacious in dissipating hydrogen peroxide (p in vitro . Our results also demonstrate that (PVPON/TA)-encapsulated islets can significantly attenuate Ifng , Cxcl10 , and Ccl5 chemokine mRNA accumulation ( p (p . In vivo, (PVPON/TA)-encapsulated islets restored euglycemia after transplantation into STZ-treated diabetic mice and demonstrated some protection against both allo- and autoimmune responses with delayed rejection times by more than thirty days in the encapsulated islet transplant recipients. Our results support the hypothesis that (PVPON/TA)-encapsulated islets may suppress immune responses and enhance islet allograft acceptance in patients with T1D. Our future studies will further determine the efficacy of (PVPON/TA)-encapsulated islets to decrease allo-, xeno-, and autoreactive immune responses in mouse models of islet transplantation.