Erythropoietin-Modified Mesenchymal Stem Cells Enhance Anti-fibrosis Efficacy in Mouse Liver Fibrosis Model

Wang, Xianyao; Wang, Huizhen; Lu, Junhou; Feng, Zhanhui; Liu, Zhongshan; Song, Hailiang; Wang, Heng; Zhou, Yanhua; Xu, Jianwei

BACKGROUND: Mesenchymal stem cell (MSC)-based cell transplantation is an effective means of treating chronic liver injury, fibrosis and end-stage liver disease. However, extensive studies have found that only a small number of transplanted cells migrate to the site of injury or lesion, and repair efficacy is very limited. METHODS: Bone marrow-derived MSCs (BM-MSCs) were generated that overexpressed the erythropoietin (EPO) gene using a lentivirus. Cell Counting Kit-8 was used to detect the viability of BM-MSCs after overexpressing EPO. Cell migration and apoptosis were verified using Boyden chamber and flow cytometry, respectively. Finally, the anti-fibrosis efficacy of EPO-MSCs was evaluated in vivo using immunohistochemical analysis. RESULTS: EPO overexpression promoted cell viability and migration of BM-MSCs without inducing apoptosis, and EPO-MSC treatment significantly alleviated liver fibrosis in a carbon tetrachloride (CCl(4)) induced mouse liver fibrosis model. CONCLUSION: EPO-MSCs enhance anti-fibrotic efficacy, with higher cell viability and stronger migration ability compared with treatment with BM-MSCs only. These findings support improving the efficiency of MSCs transplantation as a potential therapeutic strategy for liver fibrosis.