title: Differential effects of progenitor cell populations on left ventricular remodeling and myocardial neovascularization after myocardial infarction.
abstract: OBJECTIVE
  We compared biological repair after acute myocardial infarction (AMI) with selected porcine progenitor cell populations.
  
  
  BACKGROUND
  Cell types and mechanisms responsible for myocardial repair after AMI remain uncertain.
  
  
  METHODS
  In a blinded, randomized study, we infused autologous late-outgrowth endothelial progenitor cells (EPC) (n = 10, 34 +/- 22 x 10(6) CD29-31-positive, capable of tube formation), allogeneic green fluorescent peptide-labeled mesenchymal stem cells (MSC) (n = 11, 10 +/- 2 x 10(6) CD29-44-90-positive, capable of adipogenic and osteogenic differentiation), or vehicle (CON) (n = 12) in the circumflex artery 1 week after AMI. Systolic function (ejection fraction), left ventricular (LV) end-diastolic and end-systolic volumes, and infarct size were assessed with magnetic resonance imaging at 1 week and 7 weeks. Cell engraftment and vascular density were evaluated on postmortem sections.
  
  
  RESULTS
  Recovery of LV ejection fraction from 1 to 7 weeks was similar between groups, but LV remodeling markedly differed with a greater increase of LV end-systolic volume in MSC and CON (+11 +/- 12 ml/m(2) and +7 +/- 8 ml/m(2) vs. -3 +/- 11 ml/m(2) in EPC, respectively, p = 0.04), and a similar trend was noted for LV end-diastolic volume (p = 0.09). After EPC, infarct size decreased more in segments with >50% infarct transmurality (p = 0.02 vs. MSC and CON) and was associated with a greater vascular density (p = 0.01). Late outgrowth EPCs secrete higher levels of the pro-angiogenic placental growth factor (733 [277 to 1,214] pg/10(6) vs. 59 [34 to 88] pg/10(6) cells in MSC, p = 0.03) and incorporate in neovessels in vivo.
  
  
  CONCLUSIONS
  Infusion of late-outgrowth EPCs after AMI improves myocardial infarction remodeling via enhanced neovascularization but does not mediate cardiomyogenesis. Endothelial progenitor cell transfer might hold promise for heart failure prevention via pro-angiogenic or paracrine matrix-modulating effects.
authors.affiliation: Department of Cardiovascular Diseases, Gasthuisberg University Hospitals Leuven, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Dubois
authors.forename: Xiaoshun
authors.initials: X
authors.lastname: Liu
authors.forename: Piet
authors.initials: P
authors.lastname: Claus
authors.forename: Glenn
authors.initials: G
authors.lastname: Marsboom
authors.forename: Peter
authors.initials: P
authors.lastname: Pokreisz
authors.forename: Sara
authors.initials: S
authors.lastname: Vandenwijngaert
authors.forename: Hélène
authors.initials: H
authors.lastname: Dépelteau
authors.forename: Witold
authors.initials: W
authors.lastname: Streb
authors.forename: Lertlak
authors.initials: L
authors.lastname: Chaothawee
authors.forename: Frederik
authors.initials: F
authors.lastname: Maes
authors.forename: Olivier
authors.initials: O
authors.lastname: Gheysens
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Hilde
authors.initials: H
authors.lastname: Gillijns
authors.forename: Marijke
authors.initials: M
authors.lastname: Pellens
authors.forename: Thierry
authors.initials: T
authors.lastname: Vandendriessche
authors.forename: Marinee
authors.initials: M
authors.lastname: Chuah
authors.forename: Desiré
authors.initials: D
authors.lastname: Collen
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.forename: Ann
authors.initials: A
authors.lastname: Belmans
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Jan
authors.initials: J
authors.lastname: Bogaert
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007150:Immunohistochemistry; D007763:Lac Operon / Q000502:physiology; D019028:Magnetic Resonance Imaging, Cine; D020782:Matrix Metalloproteinases / Q000097:blood; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D009203:Myocardial Infarction / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D018919:Neovascularization, Physiologic / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D020782:Matrix Metalloproteinases