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

Tissue Engineering and Regenerative Medicine 2020년 17권 5호 p.683 ~ 693
Wang Xianyao, Wang Huizhen, Lu Junhou, Feng Zhanhui, Liu Zhongshan, Song Hailiang, Wang Heng, Zhou Yanhua, Xu Jianwei,
소속 상세정보
 ( Wang Xianyao ) - Guizhou Medical University Center for Tissue Engineering and Stem Cell Research
 ( Wang Huizhen ) - Nanyang Medical College Department of Stomatology
 ( Lu Junhou ) - Soochow University Medical College Department of Cell Biology
 ( Feng Zhanhui ) - Guizhou Medical University Affiliated Hospital Neurological Department
 ( Liu Zhongshan ) - Guizhou Medical University Affiliated Hospital Department of Burn and Plastic Surgery
 ( Song Hailiang ) - Dalang Hospital Department of General Surgery
 ( Wang Heng ) - Qiannan Medical College for Nationalities Department of Pharmacology
 ( Zhou Yanhua ) - Guizhou Medical University Center for Tissue Engineering and Stem Cell Research
 ( Xu Jianwei ) - Guizhou Medical University Center for Tissue Engineering and Stem Cell Research

Abstract


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 (CCl4) 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.

키워드

BM-MSCs; Erythropoietin; Migration; Anti-fibrosis efficacy; Liver fibrosis

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