title: CXCR4 gene transfer contributes to in vivo reendothelialization capacity of endothelial progenitor cells.
abstract: OBJECTIVE
  Endothelial progenitor cells (EPCs) play a pivotal role in endothelial repair after artery injury. The chemokine receptor CXCR4 is a key modulator of the homing of EPCs to impaired artery and reendothelialization. In this study, we addressed the hypothesis that CXCR4 gene transfer could enhance the reendothelialization capacity of EPCs.
  
  
  RESULTS
  In vitro, human EPCs were expanded and transduced with adenovirus serotype 5 encoding the human CXCR4 gene (Ad5/CXCR4). In vitro, CXCR4 gene transfer augmented EPC migration and enhanced EPC adhesion to endothelial cell monolayers. Adhesion assays under flow conditions showed that CXCR4 gene transfer increased the ability of EPCs to arrest on fibronectin. To determine whether CXCR4 gene transfer facilitated therapeutic reendothelialization, the effect of EPCs on in vivo reendothelialization was examined in nude mice subjected to carotid artery injury. Compared with the vehicle, transplantation of EPCs with or without gene transfer significantly accelerated in vivo reendothelialization; however, transplantation of EPCs transduced with Ad5/CXCR4 had a further enhanced effect compared with control EPCs containing EPCs transduced with an adenovirus encoding enhanced green fluorescent protein gene or non-transduced EPCs. We also found that phosphorylation of Janus kinase-2 (JAK-2), a CXCR4 downstream signalling target, was increased in EPCs transduced with Ad5/CXCR4. The enhanced in vitro function and in vivo reendothelialization capacity of EPCs by CXCR4 gene transfer were abolished by neutralizing antibodies against CXCR4 or/and JAK-2 inhibitor AG490.
  
  
  CONCLUSIONS
  The present study demonstrates that CXCR4 gene transfer contributes to the enhanced in vivo reendothelialization capacity of EPCs. Up-regulation of CXCR4 in human EPCs may become a novel therapeutic target for endothelial repair.
authors.affiliation: Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.forename: Wen-hao
authors.initials: WH
authors.lastname: Xia
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Shi-yue
authors.initials: SY
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Cheng
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Xiao-yu
authors.initials: XY
authors.lastname: Zhang
authors.forename: Shen-ming
authors.initials: SM
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000818:Animals; D002339:Carotid Arteries / Q000166:cytology* / Q000502:physiology; D020212:Carotid Artery Injuries / Q000628:therapy*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D053614:Janus Kinase 2 / Q000502:physiology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D053614:Janus Kinase 2