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Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation
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Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation
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Journal Article
Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation
2012
Overview
Objective： Mesenchymal stem cell （MSC） transplantation is a promising therapy for ischemic heart diseases. However, poor cell survival after transplantation greatly limits the therapeutic efficacy of MSCs. The purpose of this study was to investigate the protective effect of angiopoietin-1 （Angl） preconditioning on MSC survival and sub- sequent heart function improvement after transplantation. Methods： MSCs were cultured with or without 50 ng/ml Angl in complete medium for 24 h prior to experiments on cell survival and transplantation. 3-（4,5- Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and Hoechst staining were applied to evaluate MSC survival after serum deprivation in vitro, while cell survival in vivo was detected by terminal deoxynucleotidyl trans- ferase biotin-dUPT nick end labeling （TUNEL） assay 24 and 72 h after transplantation. Heart function and infarct size were measured four weeks later by small animal echocardiography and Masson＇s trichrome staining, respectively. Results： Angl preconditioning induced Akt phosphorylation and increased expression of Bcl-2 and the ratio of Bcl-2/Bax. In comparison with non-preconditioned MSCs, Angl-preconditioned cell survival was significantly in- creased while the apoptotic rate decreased in vitro. However, the PI3K/Akt pathway inhibitor, LY294002, abrogated the protective effect of Angl preconditioning. After transplantation, the Angl-preconditioned-MSC group showed a lower death rate, smaller infarct size, and better heart functional recovery compared to the non-preconditioned-MSC group. Conclusions： Angl preconditioning enhances MSC survival, contributing to further improvement of heart function.
Publisher
SP Zhejiang University Press,Springer Nature B.V,Zhejiang University Press
Subject
Angiopoietin-1 - therapeutic use
/ Animals
/ Biomedical and Life Sciences
/ Culture Media - pharmacology
/ Enzyme Inhibitors - pharmacology
/ Mesenchymal Stem Cell Transplantation - methods
/ Myocardial Infarction - pathology
/ Rats
/ Tetrazolium Salts - pharmacology
