title: VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart.
abstract: OBJECTIVE
  The objective of this study was to investigate whether vascular endothelial growth factor (VEGF) secreted by mesenchymal stem cells (MSC) improves myocardial survival and the engraftment of implanted MSC in infarcted hearts and promotes recruitment of stem cells through paracrine release of myocardial stromal cell-derived factor-1α (SDF-1α).
  
  
  RESULTS
  VEGF-expressing MSC ((VEGF)MSC)-conditioned medium enhanced SDF-1α expression in heart slices and H9C2 cardiomyoblast cells via VEGF and the vascular endothelial growth factor receptor (VEGFR). The (VEGF)MSC-conditioned medium markedly promoted cardiac stem cell (CSC) migration at least in part via the SDF-1α/CXCR4 pathway and involved binding to VEGFR-1 and VEGFR-3. In vivo, (VEGF)MSC-stimulated SDF-1α expression in infarcted hearts resulted in massive mobilization and homing of bone marrow stem cells and CSC. Moreover, VEGF-induced SDF-1α guided the exogenously introduced CSC in the atrioventricular groove to migrate to the infarcted area, leading to a reduction in infarct size. Functional studies showed that (VEGF)MSC transplantation stimulated extensive angiomyogenesis in infarcted hearts as indicated by the expression of cardiac troponin T, CD31, and von Willebrand factor and improved the left ventricular performance, whereas blockade of SDF-1α or its receptor by RNAi or antagonist significantly diminished the beneficial effects of (VEGF)MSC.
  
  
  CONCLUSIONS
  Exogenously expressed VEGF promotes myocardial repair at least in part through SDF-1α/CXCR4-mediated recruitment of CSC.
authors.affiliation: Institute of Clinical Medicine Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. tangjm416@163.com
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Tang
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Zheng
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Yang
authors.forename: Xia
authors.initials: X
authors.lastname: Kong
authors.forename: Lin-Yun
authors.initials: LY
authors.lastname: Guo
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.forename: Yong-Zhang
authors.initials: YZ
authors.lastname: Huang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D024510:Muscle Development; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism; D020127:Recovery of Function; D012038:Regeneration; D013997:Time Factors; D014162:Transfection; D020107:Troponin T / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D016277:Ventricular Function, Left; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D017077:Culture Media, Conditioned; C486264:Cxcr4 protein, rat; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019718:Receptors, CXCR4; D020107:Troponin T; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040321:Vascular Endothelial Growth Factor Receptor-3