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

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Author:: No author available

Journal Title:: Chinese Medical Journal

Issue:: 19

DOI:: 10.3760/cma.j.issn.0366-6999.2012.19.020

Key Word:: mesenchymal stem cells;reactive oxygen species;preconditioning;angiogenesis

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

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