Key result
Intracoronary infusion of autologous bone marrow-derived mononuclear cells resulted in similar overall cell retention at 3 days and 7 days post-reperfusion (2.3% vs. 3.1%, p=0.72).
Why the study?
Does the timing of intracoronary BMMNC infusion (3 vs 7 days post-AMI) affect cell retention in relation to VCAM-1 expression in a swine model of reperfused AMI?
Does the timing of intracoronary BMMNC infusion (3 vs 7 days post-AMI) affect cell retention in relation to VCAM-1 expression in a swine model of reperfused AMI?
VCAM-1 expression peaks at 3 days post-AMI but is not the principal determinant of bone marrow-derived mononuclear cell retention, as retention rates are similar at 3 and 7 days post-AMI.
Answers are grounded in this paper and cite their sources.
Similar retention despite higher VCAM-1 at day 3 cautions against VCAM-1–targeted timing; leaves open dominant homing mechanisms in post-MI cell therapy.
BACKGROUND: Intracoronary infusion of autologous bone marrow-derived mononuclear cells (BMMNC), after acute myocardial infarction (AMI), has been shown to improve myocardial function. However, therapeutic efficacy is limited, possibly because cell retention rates are low, suggesting that optimization of cell retention might increase therapeutic efficacy. Since retention of injected BMMNC is observed only within infarcted, but not remote, myocardium, we hypothesized that adhesion molecules on activated endothelium following reperfusion are essential. Consequently, we investigated the role of vascular cell adhesion molecule 1 (VCAM-1) in BMMNC retention in swine undergoing reperfused AMI produced by 120 min of percutaneous left circumflex coronary occlusion. METHODS AND RESULTS: VCAM-1 expression in the infarct and remote region was quantified at 1, 3, 7, 14, and 35 days, post-reperfusion (n≥6 swine per group). Since expression levels were significantly higher at 3 days (2.41±0.62%) than at 7 days (0.98±0.28%; p<0.05), we compared the degree of cell retention at those time points in a follow-up study, in which an average of 43·106 autologous BMMNCs were infused intracoronary at 3, or 7 days, post-reperfusion (n = 6 swine per group) and retention was histologically quantified one hour after intracoronary infusion of autologous BMMNCs. Although VCAM-1 expression correlated with retention of BMMNC within each time point, overall BMMNC retention was similar at day 3 and day 7 (2.3±1.3% vs. 3.1±1.4%, p = 0.72). This was not due to the composition of infused bone marrow cell fractions (analyzed with flow cytometry; n = 5 per group), as cell composition of the infused BMMNC fractions was similar. CONCLUSION: These findings suggest that VCAM-1 expression influences to a small degree, but is not the principal determinant of, BMMNC retention.
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Uitterdijk et al. (2017) studied Reperfused acute myocardial infarction (n=48). Intracoronary infusion of autologous bone marrow-derived mononuclear cells (BMMNC) at 3 days post-reperfusion vs. Infusion at 7 days post-reperfusion was evaluated on Overall BMMNC retention (p=0.72). Intracoronary infusion of autologous bone marrow-derived mononuclear cells resulted in similar overall cell retention at 3 days and 7 days post-reperfusion (2.3% vs. 3.1%, p=0.72).
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