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Hydrogen peroxide preconditioning enhances the therapeutic efficacy of Wharton's Jelly mesenchymal stem cells after myocardial infarction

ZHANG Jin CHEN Guang-hui WANG Yong-wei ZHAO Jing DUAN Hai-feng LIAO Lian-ming ZHANG Xiao-zhong CHEN Yun-dai CHEN Hu

中华医学杂志(英文版)2012,Vol.125Issue(19):3472-3478,7.
中华医学杂志(英文版)2012,Vol.125Issue(19):3472-3478,7.DOI:10.3760/cma.j.issn.0366-6999.2012.19.020

Hydrogen peroxide preconditioning enhances the therapeutic efficacy of Wharton's Jelly mesenchymal stem cells after myocardial infarction

Hydrogen peroxide preconditioning enhances the therapeutic efficacy of Wharton's Jelly mesenchymal stem cells after myocardial infarction

ZHANG Jin 1CHEN Guang-hui 2WANG Yong-wei 1ZHAO Jing 3DUAN Hai-feng 2LIAO Lian-ming 4ZHANG Xiao-zhong 5CHEN Yun-dai 2CHEN Hu1

作者信息

  • 1. Department of Cardiology , Chinese People's Liberation Army General Hospital, Beijing 100853, China
  • 2. Department of Cardiology ,Affiliated Hospital, Academy of Military Medical Sciences,Beijing 100071, China
  • 3. Department of Emergency , Chinese People's Liberation Army General Hospital, Beijing 100853, China
  • 4. Department of Experimental Hematology, Institute of Radiation Medical Sciences, Academy of Military Medical Sciences, Beijing 100850, China
  • 5. Institute of Oncology, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China
  • 折叠

摘要

Abstract

Background Exposure of cells to sublethal concentrations of hydrogen peroxide (H2O2) can alleviate subsequent oxidative stress-induced apoptosis.We assessed the effects of H2O2 preconditioning on the therapeutic potential of human umbilical cord Wharton's Jelly mesenchymal stem cells (WJ-MSCs) in a murine model of myocardial infarction.Methods WJ-MSCs were incubated in the media for 2 hours with or without 200 μmol/L H2O2.Mice underwent left anterior descending coronary artery ligation,and received injection of phosphate buffered saline,1x106 WJ-MSCs,or 1x106 H2O2 preconditioned WJ-MSCs 3 hours later via tail vein.Echocardiography was performed 0,7,14 and 28 days after surgery,and the mice were euthanized on day 28 for histological analysis.In vitro cytokine concentrations in the WJ-MSC cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA).The effect of WJ-MSC cell supernatant on the migration and proliferation of endothelial cells were observed by transwell migration and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) assays.Results Echocardiographic measurements revealed a significant improvement in the left ventricular contractility of the WJ-MSCs-H2O2 group compared to the WJ-MSCs group.Histological analysis revealed increased neovascularization and reduced myocardial fibrosis in the WJ-MSCs-H2O2 group compared to the WJ-MSCs group.Pretreatment of WJ-MSCs with H2O2 increased the secretion of interleukin-6 (IL-6) into the cell culture supernatant by approximately 25-fold.The culture supernatant from WJ-MSCs-H2O2 significantly increased the migration and proliferation of endothelial cells; these effects could be blocked using an anti-lL-6 antibody.Conclusions This study demonstrates that H2O2 preconditioning significantly enhanced the therapeutic potential of WJ-MSCs,possibly by stimulating the production of IL-6 by WJ-MSCs,which may cause migration and proliferation of endothelial cells and increase neovascularization.Chin Med J 2012;125(19):3472-3478

关键词

mesenchymal stem cells/ reactive oxygen species/ preconditioning/ angiogenesis

Key words

mesenchymal stem cells/ reactive oxygen species/ preconditioning/ angiogenesis

引用本文复制引用

ZHANG Jin,CHEN Guang-hui,WANG Yong-wei,ZHAO Jing,DUAN Hai-feng,LIAO Lian-ming,ZHANG Xiao-zhong,CHEN Yun-dai,CHEN Hu..Hydrogen peroxide preconditioning enhances the therapeutic efficacy of Wharton's Jelly mesenchymal stem cells after myocardial infarction[J].中华医学杂志(英文版),2012,125(19):3472-3478,7.

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