title: Stem cell factor gene transfer promotes cardiac repair after myocardial infarction via in situ recruitment and expansion of c-kit+ cells.
abstract: BACKGROUND
  There is growing evidence that the myocardium responds to injury by recruiting c-kit(+) cardiac progenitor cells to the damage tissue. Even though the ability of exogenously introducing c-kit(+) cells to injured myocardium has been established, the capability of recruiting these cells through modulation of local signaling pathways by gene transfer has not been tested.
  
  
  OBJECTIVE
  To determine whether stem cell factor gene transfer mediates cardiac regeneration in a rat myocardial infarction model, through survival and recruitment of c-kit(+) progenitors and cell-cycle activation in cardiomyocytes, and explore the mechanisms involved.
  
  
  RESULTS
  Infarct size, cardiac function, cardiac progenitor cells recruitment, fibrosis, and cardiomyocyte cell-cycle activation were measured at different time points in controls (n=10) and upon stem cell factor gene transfer (n=13) after myocardial infarction. We found a regenerative response because of stem cell factor overexpression characterized by an enhancement in cardiac hemodynamic function: an improvement in survival; a reduction in fibrosis, infarct size and apoptosis; an increase in cardiac c-kit(+) progenitor cells recruitment to the injured area; an increase in cardiomyocyte cell-cycle activation; and Wnt/β-catenin pathway induction.
  
  
  CONCLUSIONS
  Stem cell factor gene transfer induces c-kit(+) stem/progenitor cell expansion in situ and cardiomyocyte proliferation, which may represent a new therapeutic strategy to reverse adverse remodeling after myocardial infarction.
authors.affiliation: Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Yaniz-Galende
authors.forename: Jiqiu
authors.initials: J
authors.lastname: Chen
authors.forename: Elie
authors.initials: E
authors.lastname: Chemaly
authors.forename: Lifan
authors.initials: L
authors.lastname: Liang
authors.forename: Jean-Sebastien
authors.initials: JS
authors.lastname: Hulot
authors.forename: LaTronya
authors.initials: L
authors.lastname: McCollum
authors.forename: Teresa
authors.initials: T
authors.lastname: Arias
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.forename: Krisztina M
authors.initials: KM
authors.lastname: Zsebo
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D049109:Cell Proliferation; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D018613:Microscopy, Confocal; D009203:Myocardial Infarction / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D019089:Stem Cell Factor; D051176:beta Catenin; D019009:Proto-Oncogene Proteins c-kit