title: Transmyocardial revascularization induces mesenchymal stem cell engraftment in infarcted hearts.
abstract: BACKGROUND
  Transmyocardial revascularization (TMR) prior to mesenchymal stem cell (MSC) transplantation augments repair of infarcted hearts. We evaluated the effects of TMR on homing and engraftment of circulating MSCs and mediators of this effect.
  
  
  METHODS
  Three weeks after left anterior descending coronary artery ligation in female rats, 10-channel needle TMR was performed in the infarct, followed by daily intravenous injections of 1 million male MSCs for 5 days. Control rats had MSC infusions without TMR (n=16/group). Donor MSC survival was evaluated at 3 days and at 1 week by quantitative polymerase chain reaction, as well as expression of stem cell factor (SCF), stromal derived factor-1 (SDF-1), c-kit, and chemokine receptor type 4 (CXCR4).
  
  
  RESULTS
  The MSCs engrafted into the infarct, clustering around TMR channels. The MSC engraftment was greater in TMR hearts at 3 days and at 1 week. Both SCF (p=0.03) and c-kit (p=0.01) were upregulated by TMR at 3 days, but their levels fell at 1 week (p=0.3, p=0.5, respectively). The SDF-1 levels were higher in TMR hearts at both 3 days (p=0.04) and at 1 week (p=0.04). The CXCR4 was upregulated early by TMR (p=0.0002) but levels dropped dramatically at 1 week (p=0.045).
  
  
  CONCLUSIONS
  Transmyocardial revascularization induces transmigration and engraftment of circulating MSCs. Post TMR, the transcription of SCF and c-kit is rapid and corresponds temporally to MSC engraftment, while SDF-1 levels rise slowly. The CXCR4 is also transiently upregulated. The TMR-augmented repair of infarcted hearts by stem cell transplantation may be mediated by a novel mechanism: transmigration and engraftment of circulating progenitor cells.
authors.affiliation: Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, University Health Network, Department of Surgery, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Uswa
authors.initials: U
authors.lastname: Shahzad
authors.forename: Guangming
authors.initials: G
authors.lastname: Li
authors.forename: Yaoguang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Yau
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D059630:Mesenchymal Stem Cells; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery*; D009204:Myocardial Revascularization / Q000009:adverse effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar