Key result
Late-outgrowth EPCs improve post-AMI LV remodeling vs MSCs and vehicle, reducing end-systolic volume by ~3 ml/m2.
Why the study?
The specific cell types and biological mechanisms responsible for myocardial repair after acute myocardial infarction remained uncertain.
RCT (n=33)
blinded
randomized
Answers are grounded in this paper and cite their sources.
Comparative study reveals differential impacts of progenitor cell types on ventricular remodeling and neovascularization after myocardial infarction, indicating distinct therapeutic mechanisms.
OBJECTIVES: 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.
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Dubois et al. (2010) conducted an RCT in acute myocardial infarction (AMI) (n=33). Autologous late-outgrowth endothelial progenitor cells (EPC) vs. Allogeneic mesenchymal stem cells (MSC) or vehicle (CON) was evaluated on Change in left ventricular end-systolic volume from 1 to 7 weeks (p=0.04). Infusion of late-outgrowth EPCs after AMI improved LV remodeling compared to MSCs and vehicle, evidenced by a reduction in LV end-systolic volume (-3 vs +11 and +7 ml/m2, p=0.04).
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