title: Comparative effects of mesenchymal progenitor cells, endothelial progenitor cells, or their combination on myocardial infarct regeneration and cardiac function.
abstract: OBJECTIVE
  Recent evidence suggests that the effects of mesenchymal progenitor cell transplantation into the infarcted myocardium might be mediated by local paracrine angiogenesis. We compared the effects of mesenchymal progenitor cell transplantation versus those of a primarily angiogenic cell, the endothelial progenitor cell, in a rat model of myocardial infarction.
  
  
  METHODS
  Twenty-one days after left anterior descending artery ligation, rats were injected in their infarcted anterior myocardium with 1 x 10(6) mesenchymal progenitor cells, 1 x 10(6) endothelial progenitor cells, 5 x 10(5) mesenchymal progenitor cells plus 5 x 10(5) endothelial progenitor cells, or phosphate-buffered saline (n = 6-8 per group). Echocardiography was performed before injection and 4 weeks later, after which rats were killed and immunohistochemical analyses performed.
  
  
  RESULTS
  Connexin43 density was greater in cell-treated groups compared with that seen in the phosphate-buffered saline group (by 91.6% +/- 15.2%, P < .001), with no observed difference between cell-treated groups (P > or = .3). Endothelial progenitor cell treatment increased arteriolar density within the infarct border zone (by 297%, 205%, and 101% vs phosphate-buffered saline, mesenchymal progenitor cell, and mesenchymal progenitor cell/endothelial progenitor cell treatment, respectively; P < .01). Postoperative left ventricular ejection fraction (endothelial progenitor cell: 68.3% +/- 9.8% vs mesenchymal progenitor cell/endothelial progenitor cell: 55.0% +/- 11.1%, mesenchymal progenitor cell: 53.0% +/- 6.0%, and phosphate-buffered saline: 49.6% +/- 9.5%) and fractional shortening (endothelial progenitor cell: 32.4% +/- 5.1% vs mesenchymal progenitor cell: 22.5% +/- 5.4% and phosphate-buffered saline: 21.3% +/- 5.3%) were greater in endothelial progenitor cell-treated rats versus those receiving other treatments (all P < .05). Only endothelial progenitor cells prevented further contractile deterioration compared with baseline values (P = .8), whereas other groups had continued loss of function after treatment.
  
  
  CONCLUSIONS
  Compared with the use of mesenchymal progenitor cells, cell transplantation with endothelial progenitor cells after myocardial infarction resulted in better neovascularization and contractility. This suggests that angiogenesis is an important mechanism in attenuating the progression of left ventricular dysfunction after myocardial infarction.
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
authors.forename: Joel
authors.initials: J
authors.lastname: Price
authors.forename: John P
authors.initials: JP
authors.lastname: Veinot
authors.forename: Kathryn
authors.initials: K
authors.lastname: Ascah
authors.forename: Varun
authors.initials: V
authors.lastname: Kapila
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Guo
authors.forename: Serena
authors.initials: S
authors.lastname: Wong
authors.forename: Thierry G
authors.initials: TG
authors.lastname: Mesana
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D004452:Echocardiography; D042783:Endothelial Cells / Q000637:transplantation*; D006321:Heart / Q000502:physiology*; D015552:Injections, Intralesional; D045164:Mesenchymal Stem Cell Transplantation; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods*; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D016277:Ventricular Function, Left