Differential Effects of Progenitor Cell Populations on Left Ventricular Remodeling and Myocardial Neovascularization After Myocardial Infarction

ObjectivesWe compared biological repair after acute myocardial infarction (AMI) with selected porcine progenitor cell populations.BackgroundCell types and mechanisms responsible for myocardial repair after AMI remain uncertain.MethodsIn a blinded, randomized study, we infused autologous late-outgrowth endothelial progenitor cells (EPC) (n = 10, 34 ± 22 × 106CD29-31-positive, capable of tube formation), allogeneic green fluorescent peptide–labeled mesenchymal stem cells (MSC) (n = 11, 10 ± 2 × 106CD29-44-90-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.ResultsRecovery 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/m2and +7 ± 8 ml/m2vs. −3 ± 11 ml/m2in 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/106vs. 59 [34 to 88] pg/106cells in MSC, p = 0.03) and incorporate in neovessels in vivo.ConclusionsInfusion 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