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

硫酸化海藻酸盐可减少小鼠 cGMP 兼容 hPSC 肝细胞的包膜周围纤维化过度生长

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作者: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

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.

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