Authors:
Dana Pham-Hua1, 2, 3, 4
Lindsey Padgett1, 2
Bing Xue3
Veronika Kozlovskaya3
Eugenia Kharlampieva3
Hubert Tse1,2
Departments:
1. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
2. Comprehensive Diabetes Center, University of Alabamaat Birmingham, Birmingham, AL, USA
3. Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, USA
4. Science and Technology Honors Program, University of Alabama at Birmingham, Birmingham, AL, USA
Abstract
Type 1 Diabetes (T1D) is a chronic pro-inflammatory autoimmune disease consisting of reactive oxygen species (ROS), pro-inflammatory cytokines, and islet-infiltrating leukocytes involved in pancreatic β-cell lysis. One promising treatment for T1D is islet transplantation; however, its clinical application is constrained due to limited islet availability, adverse effects of immunosuppressants on islet function, and declining graft survival. Islet encapsulation may provide an immunoprotective barrier to help preserve islet function and prevent immune-mediated rejection after transplantation into T1D patients. Wepreviously demonstrated that a novel cytoprotective nanothin coating for islet encapsulation consisting of tannic acid (TA), an immunomodulatory antioxidant, and poly N-vinylpyrrolidone (PVPON), was efficacious in dampening diabetogenic CD4 T cell and macrophage responses involved in transplant rejection. Therefore, we hypothesized that in addition to suppressing pro-inflammatory cytokine synthesis, TA/PVPON would similarly blunt the production of pro-inflammatory chemokines involved in recruiting immune cells to the site of islet engraftment. Our results provide further support that TA/PVPON-containing encapsulated islets are effective in suppressing pro-inflammatory CCL5 and CXCL10 chemokine synthesis. The use of novel TA/PVPON nanothin coatings may potentially decrease immune-mediated responses and enhance islet allo-and xenograft acceptance to restore euglycemia in T1D patients.