The therapeutic effect and mechanism of CXCL9-overexpressed umbilical cord mesenchymal stem cells on liver fibrosis

Abstract

Umbilical cord mesenchymal stem cells (UC-MSC) transplantation has become a promising treatment for liver fibrosis. However, UC-MSC have limited anti-fibrosis ability for various reasons. In this study, we aimed to determine if the overexpression of CXCL9 in UC-MSC (CXCL9-UC-MSCs) could have synergistic anti-fibrosis effects and explore the possible mechanism. We analyzed the expression of α-SMA and Collagen-III in rats and LX-2 cells, as well as the inhibition of the TGF-β1/Smad3 pathway, approched by staining HE staining, immunohistochemistry staining, and western-blot. After the cell therapy, pathological staining and liver function indicated that the area of liver fibrosis in the rats were reduced, the hepatocellular necrosis and liver function damage were improved, and the improvement was more significant in the CXCL9-UC-MSC intervention group. Furthermore, the expression levels of α-SMA, Collagen-III, TGF-β1 and pSmad3 in the liver and LX-2 cells were decreased more obviously atfer the CXCL9 intervention. Meanwhile, the abilities of proliferation, viability and invasiveness of LX-2 cells were also significantly inhibited with the intervention of CXCL9. In conclusion, CXCL9 overexpression of UC-MSC inhibited the activation of TGF-β1/Smad3 signaling pathway, and reduced the expressions of α-SMA and Collagen-III in liver and LX-2 cells, thus playing a more significant anti-fibrosis effect.