Dataset Information

Time course of VCAM-1 expression in reperfused myocardial infarction in swine and its relation to retention of intracoronary administered bone marrow-derived mononuclear cells.

ABSTRACT:

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.

SUBMITTER: Uitterdijk A

PROVIDER: S-EPMC5476248 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Time course of VCAM-1 expression in reperfused myocardial infarction in swine and its relation to retention of intracoronary administered bone marrow-derived mononuclear cells.

Uitterdijk André A Groenendijk Bianca C W BCW Gorsse-Bakker Charlotte C Panasewicz Anna A Sneep Stefan S Tempel Dennie D van de Kamp Esther H EH Merkus Daphne D van der Giessen Willem J WJ Duncker Dirk J DJ

PloS one 20170619 6

<h4>Background</h4>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 ...[more]

PMID: 28628621

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Project description:Background:Intracoronary (IC) injection of mesenchymal stem cells (MSCs) results in a prompt decrease of absolute myocardial blood flow (AMF) with late and incomplete recovery of myocardial tissue perfusion. Here, we investigated the effect of decreased AMF on oxidative stress marker matrix metalloproteinase-2 (MMP-2) and its influence on the fate and homing and paracrine character of MSCs after IC or intramyocardial cell delivery in a closed-chest reperfused myocardial infarction (MI) model in pigs. Methods:Porcine MSCs were transiently transfected with Ad-Luc and Ad-green fluorescent protein (GFP). One week after MI, the GFP-Luc-MSCs were injected either IC (group IC, 11.00?±?1.07?×?106) or intramyocardially (group IM, 9.88?±?1.44?×?106). AMF was measured before, immediately after, and 24?h post GFP-Luc-MSC delivery. In vitro bioluminescence signal was used to identify tissue samples containing GFP-Luc-MSCs. Myocardial tissue MMP-2 and CXCR4 receptor expression (index of homing signal) were measured in bioluminescence positive and negative infarcted and border, and non-ischemic myocardial areas 1-day post cell transfer. At 7-day follow-up, myocardial homing (cadherin, CXCR4, and stromal derived factor-1alpha) and angiogenic [fibroblast growth factor 2 (FGF2) and VEGF] were quantified by ELISA of homogenized myocardial tissues from the bioluminescence positive and negative infarcted and border, and non-ischemic myocardium. Biodistribution of the implanted cells was quantified by using Luciferase assay and confirmed by fluorescence immunochemistry. Global left ventricular ejection fraction (LVEF) was measured at baseline and 1-month post cell therapy using magnet resonance image. Results:AMF decreased immediately after IC cell delivery, while no change in tissue perfusion was found in the IM group (42.6?±?11.7 vs. 56.9?±?16.7?ml/min, p?=?0.018). IC delivery led to a significant increase in myocardial MMP-2 64?kD expression (448?±?88 vs. 315?±?54 intensity?×?mm2, p?=?0.021), and decreased expression of CXCR4 (592?±?50 vs. 714?±?54?pg/tissue/ml, p?=?0.006), with significant exponential decay between MMP-2 and CXCR4 (r?=?0.679, p?<?0.001). FGF2 and VEGF of the bioluminescence infarcted and border zone of homogenized tissues were significantly elevated in the IM goups as compared to IC group. LVEF increase was significantly higher in IM group (0.8?±?8.4 vs 5.3?±?5.2%, p?=?0.046) at the 1-month follow up. Conclusion:Intracoronary stem cell delivery decreased AMF, with consequent increase in myocardial expression of MMP-2 and reduced CXCR4 expression with lower level of myocardial homing and angiogenic factor release as compared to IM cell delivery.

Dataset Information

Time course of VCAM-1 expression in reperfused myocardial infarction in swine and its relation to retention of intracoronary administered bone marrow-derived mononuclear cells.

Background

Methods and results

Conclusion

Publications

Time course of VCAM-1 expression in reperfused myocardial infarction in swine and its relation to retention of intracoronary administered bone marrow-derived mononuclear cells.

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