title: Human blood and cardiac stem cells synergize to enhance cardiac repair when cotransplanted into ischemic myocardium.
abstract: BACKGROUND
  Blood-derived circulatory angiogenic cells (CACs) and resident cardiac stem cells (CSCs) have both been shown to improve cardiac function after myocardial infarction. The superiority of either cell type has long been an area of speculation with no definitive head-to-head trial. In this study, we compared the effect of human CACs and CSCs, alone or in combination, on myocardial function in an immunodeficient mouse model of myocardial infarction.
  
  
  RESULTS
  CACs and CSCs were cultured from left atrial appendages and blood samples obtained from patients undergoing clinically indicated heart surgery. CACs expressed a broader cytokine profile than CSCs, with 3 cytokines in common. Coculture of CACs and CSCs further enhanced the production of stromal cell-derived factor-1α and vascular endothelial growth factor (P ≤ 0.05). Conditioned media promoted equivalent vascular networks and CAC recruitment with superior effects using cocultured conditioned media. Intramyocardial injection of CACs or CSCs alone improved myocardial function and reduced scar burdens when injected 1 week after myocardial infarction (P ≤ 0.05 versus negative controls). Cotransplantation of CACs and CSCs together improved myocardial function and reduced scar burdens to a greater extent than either stem cell therapy alone (P ≤ 0.05 versus CAC or CSC injection alone).
  
  
  CONCLUSIONS
  CACs and CSCs provide unique paracrine repertoires with equivalent effects on angiogenesis, stem cell migration, and myocardial repair. Combination therapy with both cell types synergistically improves postinfarct myocardial function greater than either therapy alone. This synergy is likely mediated by the complimentary paracrine signatures that promote revascularization and the growth of new myocardium.
authors.affiliation: University of Ottawa Heart Institute, Department of Cardiology, Ottawa, Ontario, Canada (N.L., B.Y., R.J., B.-K.L., D.K., M.R., E.J.S., D.R.D.); and Ottawa Hospital Research Institute, Department of Medicine, Ottawa, Ontario, Canada (D.J.S.).
authors.forename: Nicholas
authors.initials: N
authors.lastname: Latham
authors.forename: Bin
authors.initials: B
authors.lastname: Ye
authors.forename: Robyn
authors.initials: R
authors.lastname: Jackson
authors.forename: Bu-Khanh
authors.initials: BK
authors.lastname: Lam
authors.forename: Drew
authors.initials: D
authors.lastname: Kuraitis
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: Darryl R
authors.initials: DR
authors.lastname: Davis
mesh_terms: D000368:Aged; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D017202:Myocardial Ischemia / Q000473:pathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology* / Q000637:transplantation*; D018919:Neovascularization, Physiologic / Q000502:physiology; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000473:pathology / Q000502:physiology*
keywords: blood cells; heart failure; myocardial infarction; stem cells
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