Tissue Eng Regen Med.  2020 Oct;17(5):683-693. 10.1007/s13770-020-00276-2.

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

Affiliations
  • 1National 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
  • 2Key Laboratory of Adult Stem Cell Translational Research, Chinese Academy of Medical Sciences, Guiyang 550004, China
  • 3Department of Immunology, School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China
  • 4Department of Stomatology, Nanyang Medical College, Nanyang 473000, China
  • 5Department of Cell Biology, Medical College of Soochow University, Suzhou 215123, China
  • 6Neurological Department, Affiliated Hospital of Guizhou Medical University, Guiyang 550025, China
  • 7Department of Burn and Plastic Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang 550025, China
  • 8Department of General Surgery, Dalang Hospital, Dongguan 523000, China
  • 9Department of Pharmacology, Qiannan Medical College for Nationalities, Duyun 558000, China
  • 10Department of Pharmacology, School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China

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.

Keyword

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