title: Islet encapsulation with polyphenol coatings decreases pro-inflammatory chemokine synthesis and T cell trafficking.
abstract: Type 1 Diabetes (T1D) is a chronic pro-inflammatory autoimmune disease consisting of islet-infiltrating leukocytes involved in pancreatic β-cell lysis. One promising treatment for T1D is islet transplantation; however, 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 preserve islet function and prevent immune-mediated rejection after transplantation. We previously demonstrated that a novel cytoprotective nanothin multilayer coating for islet encapsulation consisting of tannic acid (TA), an immunomodulatory antioxidant, and poly(N-vinylpyrrolidone) (PVPON), was efficacious in dampening in vitro immune responses involved in transplant rejection and preserving in vitro islet function. However, the ability of (PVPON/TA) to maintain islet function in vivo and reverse diabetes has not been tested. Recent evidence has demonstrated that modulation of redox status can affect pro-inflammatory immune responses. Therefore, we hypothesized that transplanted (PVPON/TA)-encapsulated islets can restore euglycemia to diabetic mice and provide an immunoprotective barrier. Our results demonstrate that (PVPON/TA) nanothin coatings can significantly decrease in vitro chemokine synthesis and diabetogenic T cell migration. Importantly, (PVPON/TA)-encapsulated islets restored euglycemia after transplantation into diabetic mice. Our results demonstrate that (PVPON/TA)-encapsulated islets may suppress immune responses and enhance islet allograft acceptance in patients with T1D.
authors.affiliation: Science Technology Honors Program, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Pham-Hua
authors.affiliation: Department of Microbiology, Comprehensive Diabetes Center, University of Alabama, Birmingham School of Medicine, Birmingham, AL 35294-2182, USA.
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: Padgett
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Microbiology, Comprehensive Diabetes Center, University of Alabama, Birmingham School of Medicine, Birmingham, AL 35294-2182, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Anderson
authors.affiliation: Department of Microbiology, Comprehensive Diabetes Center, University of Alabama, Birmingham School of Medicine, Birmingham, AL 35294-2182, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Zeiger
authors.affiliation: Department of Microbiology, Comprehensive Diabetes Center, University of Alabama, Birmingham School of Medicine, Birmingham, AL 35294-2182, USA.
authors.forename: Jessie M
authors.initials: JM
authors.lastname: Barra
authors.affiliation: Comprehensive Diabetes Center and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.
authors.forename: Maigen
authors.initials: M
authors.lastname: Bethea
authors.affiliation: Comprehensive Diabetes Center and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.
authors.forename: Chad S
authors.initials: CS
authors.lastname: Hunter
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Kozlovskaya
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA; Center of Nanoscale Materials and Biointegration, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA. Electronic address: ekharlam@uab.edu.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Kharlampieva
authors.affiliation: Department of Microbiology, Comprehensive Diabetes Center, University of Alabama, Birmingham School of Medicine, Birmingham, AL 35294-2182, USA. Electronic address: htse@uab.edu.
authors.forename: Hubert M
authors.initials: HM
authors.lastname: Tse
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis*; D002633:Chemotaxis / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D011070:Poly I-C / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D015415:Biomarkers; D018925:Chemokines; D020099:Coated Materials, Biocompatible; D005609:Free Radicals; D018836:Inflammation Mediators; D059808:Polyphenols; D011760:Pyrrolidinones; C042670:N-vinyl-2-pyrrolidinone; D011070:Poly I-C
keywords: Antioxidant; Chemokines; Islet transplantation; Macrophage; Reactive oxygen species; Type 1 diabetes