Uitterdijk André, Groenendijk Bianca C W, Gorsse-Bakker Charlotte, Panasewicz Anna, Sneep Stefan, Tempel Dennie, van de Kamp Esther H, Merkus Daphne, van der Giessen Willem J, Duncker Dirk J
Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
PLoS One. 2017 Jun 19;12(6):e0178779. doi: 10.1371/journal.pone.0178779. eCollection 2017.
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.
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.
These findings suggest that VCAM-1 expression influences to a small degree, but is not the principal determinant of, BMMNC retention.
急性心肌梗死（AMI）后冠状动脉内注入自体骨髓来源的单个核细胞（BMMNC）已显示可改善心肌功能。然而，治疗效果有限，可能是因为细胞留存率低，这表明优化细胞留存可能会提高治疗效果。由于仅在梗死心肌而非远隔心肌中观察到注入的BMMNC的留存，我们推测再灌注后活化内皮细胞上的黏附分子至关重要。因此，我们研究了血管细胞黏附分子1（VCAM-1）在经皮左旋支冠状动脉闭塞120分钟产生再灌注性AMI的猪中对BMMNC留存的作用。
在再灌注后1、3、7、14和35天对梗死区和远隔区的VCAM-1表达进行定量（每组≥6头猪）。由于3天时的表达水平（2.41±0.62%）显著高于7天时（0.98±0.28%；p<0.05），我们在一项后续研究中比较了这些时间点的细胞留存程度，在该研究中，在再灌注后3天或7天冠状动脉内平均注入43×10⁶个自体BMMNC（每组n = 6头猪），并在冠状动脉内注入自体BMMNC 1小时后通过组织学方法对留存情况进行定量。尽管在每个时间点VCAM-1表达与BMMNC留存相关，但总体而言BMMNC在第3天和第7天的留存相似（2.3±1.3%对3.1±1.4%，p = 0.72）。这并非由于注入的骨髓细胞组分的构成（通过流式细胞术分析；每组n = 5），因为注入的BMMNC组分的细胞构成相似。
这些发现表明VCAM-1表达对BMMNC留存有一定程度的影响，但不是主要决定因素。
