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

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

doi:10.3389/fbioe.2021.816542

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.

Highlights

The liver is one of the most important organs in the body providing numerous vital physiological functions, including protein synthesis, drug metabolism and detoxification, and macronutrient processing (Worman, 1995)
Progress has been made in the development of alternative approaches to the treatment of acute liver failure (ALF), including allogeneic hepatocyte transplantation (Dhawan et al, 2010)
As the sulfation destroys the specific crosslinking of divalent ions by the blocks of consecutive G-units, the sulfated alginate was mixed with non-modified alginate to maintain the gelling capacity (Arlov et al, 2014)

Summary

Introduction

The liver is one of the most important organs in the body providing numerous vital physiological functions, including protein synthesis, drug metabolism and detoxification, and macronutrient processing (Worman, 1995). The only curative therapy for acute liver failure (ALF) and end-stage liver disease (ESLD) patients is orthotopic liver transplantation (Asrani et al, 2019). The pool of eligible organ donors is often very limited, which raises the mortality rates of patients affected by ALF that await an HLA-compatible donor (Bernal et al, 2009). Progress has been made in the development of alternative approaches to the treatment of ALF, including allogeneic hepatocyte transplantation (Dhawan et al, 2010). Despite that this mode of treatment does not require an entire donor liver, there are still some limitations such as obtaining optimal quality of hepatocytes from the source and donor suitability

Methods

Results

Conclusion