Sulfated Alginate Reduces Pericapsular Fibrotic Overgrowth on Encapsulated cGMP-Compliant hPSC-Hepatocytes in Mice

Adam M Syanda; Vera I Kringstad; Samuel J I Blackford; Joachim S Kjesbu; Soon Seng Ng; Liang Ma; Fang Xiao; Abba E Coron; Anne Mari A Rokstad; Sunil Modi; S Tamir Rashid; Berit Løkensgard Strand

doi:10.3389/fbioe.2021.816542

Sulfated Alginate Reduces Pericapsular Fibrotic Overgrowth on Encapsulated cGMP-Compliant hPSC-Hepatocytes in Mice

Front Bioeng Biotechnol. 2022 Mar 3:9:816542. doi: 10.3389/fbioe.2021.816542. eCollection 2021.

Affiliations

¹ Department of Metabolism, Digestion and Reproduction, Imperial College London (ICL), London, United Kingdom.
² Department of Biotechnology and Food Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
³ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Abstract

Intra-peritoneal placement of alginate encapsulated human induced pluripotent stem cell-derived hepatocytes (hPSC-Heps) represents a potential new bridging therapy for acute liver failure. One of the rate-limiting steps that needs to be overcome to make such a procedure more efficacious and safer is to reduce the accumulation of fibrotic tissue around the encapsulated cells to allow the free passage of relevant molecules in and out for metabolism. Novel chemical compositions of alginate afford the possibility of achieving this aim. We accordingly used sulfated alginate and demonstrated that this material reduced fibrotic overgrowth whilst not impeding the process of encapsulation nor cell function. Cumulatively, this suggests sulfated alginate could be a more suitable material to encapsulate hPSC-hepatocyte prior to human use.

Keywords: PFO; acute liver failure; cGMP; hPSC; immunogenicity; immunoisolation; pluripotent stem cell-derived hepatocytes; sulfated alginate.