Differential effects of progenitor cell populations on left ventricular remodeling and myocardial neovascularization after myocardial infarction.
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.
Dubois
Christophe
C
Department of Cardiovascular Diseases, Gasthuisberg University Hospitals Leuven, Leuven, Belgium.
Liu
Xiaoshun
X
Claus
Piet
P
Marsboom
Glenn
G
Pokreisz
Peter
P
Vandenwijngaert
Sara
S
Dépelteau
Hélène
H
Streb
Witold
W
Chaothawee
Lertlak
L
Maes
Frederik
F
Gheysens
Olivier
O
Debyser
Zeger
Z
Gillijns
Hilde
H
Pellens
Marijke
M
Vandendriessche
Thierry
T
Chuah
Marinee
M
Collen
Desiré
D
Verbeken
Erik
E
Belmans
Ann
A
Van de Werf
Frans
F
Bogaert
Jan
J
Janssens
Stefan
S
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*
D020782:Matrix Metalloproteinases