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

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Online ISSN 2212-5469

ORIGINAL ARTICLE

Erythropoietin-Modified Mesenchymal Stem Cells Enhance Antifibrosis Efficacy in Mouse Liver Fibrosis Model Xianyao Wang1,2,3 • Huizhen Wang4 • Junhou Lu5 • Zhanhui Feng6 • Zhongshan Liu7 • Hailiang Song8 • Heng Wang9 • Yanhua Zhou1,2 • Jianwei Xu1,2,10

Received: 9 April 2020 / Revised: 11 May 2020 / Accepted: 22 May 2020 Ó The Korean Tissue Engineering and Regenerative Medicine Society 2020

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. Keywords BM-MSCs  Erythropoietin  Migration  Anti-fibrosis efficacy  Liver fibrosis

& Yanhua Zhou [email protected]

4

Department of Stomatology, Nanyang Medical College, Nanyang 473000, China

& Jianwei Xu [email protected]

5

Department of Cell Biology, Medical College of Soochow University, Suzhou 215123, China

6

Neurological Department, Affiliated Hospital of Guizhou Medical University, Guiyang 550025, China

7

Department of Burn and Plastic Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang 550025, China

8

Department of General Surgery, Dalang Hospital, Dongguan 523000, China

9

Department of Pharmacology, Qiannan Medical College for Nationalities, Duyun 558000, China

10

Department of Pharmacology, School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China

1

2

3

National Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique/Center for Tissue Engineering and Stem Cell Research/Guizhou Province Key Laboratory of Regenerative Medicine, Guizhou Medical University, Beijing Road 9, Guiyang 550004, Guizhou Province, China Key Laboratory of Adult Stem Cell Translational Research, Chinese Academy of Medical Sciences, Guiyang 550004, China Department of Immunology, School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China

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