Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/?-catenin pathway.

ABSTRACT: BACKGROUND:Mesenchymal stem cells (MSCs) are increasingly being applied as a therapy for liver fibrosis. Exosomes possess similar functions to their parent cells; however, they are safe and effective cell-free reagents with controllable and predictable outcomes. In this study, we investigated the therapeutic potential and underlying molecular mechanism for human bone mesenchymal stem cells-derived exosomes (hBM-MSCs-Ex) in the treatment of liver fibrosis. METHODS:We established an 8-week CCl4-induced rat liver fibrosis model, after which, we administered hBM-MSCs-Ex in vivo for 4?weeks. The resulting histopathology, liver function, and inflammatory cytokines were analyzed. In addition, we investigated the anti-fibrotic mechanism of hBM-MSCs-Ex in hepatic stellate cells (HSCs) and liver fibrosis tissue, by western blotting for the expression of Wnt/?-catenin signaling pathway-related genes. RESULTS:In vivo administration of hBM-MSCs-Ex effectively alleviated liver fibrosis, including a reduction in collagen accumulation, enhanced liver functionality, inhibition of inflammation, and increased hepatocyte regeneration. Moreover, based on measurement of the collagen area, Ishak fibrosis score, MDA levels, IL-1, and IL-6, the therapeutic effect of hBM-MSCs-Ex against liver fibrosis was significantly greater than that of hBM-MSCs. In addition, we found that hBM-MSCs-Ex inhibited the expression of Wnt/?-catenin pathway components (PPAR?, Wnt3a, Wnt10b, ?-catenin, WISP1, Cyclin D1), ?-SMA, and Collagen I, in both HSCs and liver fibrosis tissue. CONCLUSIONS:These results suggest that hBM-MSCs-Ex treatment could ameliorate CCl4-induced liver fibrosis via inhibition of HSC activation through the Wnt/?-catenin pathway.

SUBMITTER: Rong X 

PROVIDER: S-EPMC6421647 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature