Nanothin Conformal Coating with Poly(N-vinylpyrrolidone) and Tannic Acid (PVPON/TA) Preserves Murine and Human Pancreatic Islets Function

Author:

Polishevska Kateryna12,Kelly Sandra12ORCID,Kuppan Purushothaman12ORCID,Seeberger Karen L.12,Aggarwal Saloni12,Paramor Joy12,Unsworth Larry D.3,Tse Hubert M.4,Korbutt Gregory S.12ORCID,Pepper Andrew R.12ORCID

Affiliation:

1. Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2T9, Canada

2. Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada

3. Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 2E1, Canada

4. Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA

Abstract

Beta cell replacement therapies can restore glycemic control to select individuals living with type 1 diabetes. However, the obligation of lifelong immunosuppression restricts cell therapies from replacing exogenous insulin administration. Encapsulation strategies can reduce the inherent adaptive immune response; however, few are successfully translated into clinical testing. Herein, we evaluated if the conformal coating of islets with poly(N-vinylpyrrolidone) (PVPON) and tannic acid (TA) (PVPON/TA) could preserve murine and human islet function while conferring islet allograft protection. In vitro function was evaluated using static glucose-stimulated insulin secretion, oxygen consumption rates, and islet membrane integrity. In vivo function was evaluated by transplanting human islets into diabetic immunodeficient B6.129S7-Rag1tm1Mom/J (Rag-/-) mice. The immunoprotective capacity of the PVPON/TA-coating was assessed by transplanting BALB/c islets into diabetic C57BL/6 mice. Graft function was evaluated by non-fasting blood glucose measurements and glucose tolerance testing. Both coated and non-coated murine and human islets exhibited indistinguishable in vitro potency. PVPON/TA-coated and control human islets were able to restore euglycemia post-transplant. The PVPON/TA-coating as monotherapy and adjuvant to systemic immunosuppression reduced intragraft inflammation and delayed murine allograft rejection. This study demonstrates that PVPON/TA-coated islets may be clinically relevant as they retain their in vitro and in vivo function while modulating post-transplant immune responses.

Funder

JDRF Career Development Award

Alberta Diabetes Foundation Scholarship

Canada Research Chairs Program

Publisher

MDPI AG

Subject

Pharmaceutical Science

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