Human Allogeneic Liver-Derived Progenitor Cells Significantly Improve NAFLD Activity Score and Fibrosis in Late-Stage NASH Animal Model

Abstract

Accumulated experimental and clinical evidence supports the development of human allogeneic liver-derived progenitor cells (HALPCs) to treat fibro-inflammatory liver diseases. The aim of the present study was to evaluate their therapeutic effect in a non-alcoholic steatohepatitis (NASH)-STAM mouse model. The immune signaling characteristics of HALPCs were first assessed in vitro. Upon inflammation treatment, HALPCs secreted large amounts of potent bioactive prostaglandin E2 and indoleamine 2,3-dioxygenase, which significantly reduced CD4+ T-lymphocyte proliferation and secretion of proinflammatory cytokines. In vivo, HALPCs were intravenously administered as single or triple shots (of a dose of 12.5 × 106 cells/kg BW) in STAM mice. Transplantation of HALPCs was associated with a significant decrease in the NAFLD activity score at an early stage and in both inflammation and hepatocyte ballooning scores in late-stage NASH. Sirius red staining analyses revealed decreased collagen deposition in the pericentral region at both stages of NASH. Altogether, these findings showed the anti-inflammatory and anti-fibrotic features of HALPCs in an in vivo NASH model, which suggests their potential to reverse the progression of this chronic fibro-inflammatory disease.

Hepatic Macrophages as Targets for the MSC-Based Cell Therapy in Non-Alcoholic Steatohepatitis

“…A preliminary efficacy study demonstrated normalization of ALT and AST serum levels and gradual decreasing of bilirubin and triglyceride levels as well as IL-6 levels and fibrosis over a period of 6 months [177]. In the early-and late-stage NASH mouse models, these human allogeneic liver-derived progenitor cells exhibited pronounced anti-inflammatory and anti-fibrotic effects [178]. In another clinical trial (UMIN000022601), MSCs showed a significant therapeutic effect in patients with NAFLD/NASH.…”