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Matrix Metalloproteinase-2 Impairs Homing of Intracoronary Delivered Mesenchymal Stem Cells in a Porcine Reperfused Myocardial Infarction: Comparison With Intramyocardial Cell Delivery

Overview of attention for article published in Frontiers in Bioengineering and Biotechnology, April 2018
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Title
Matrix Metalloproteinase-2 Impairs Homing of Intracoronary Delivered Mesenchymal Stem Cells in a Porcine Reperfused Myocardial Infarction: Comparison With Intramyocardial Cell Delivery
Published in
Frontiers in Bioengineering and Biotechnology, April 2018
DOI 10.3389/fbioe.2018.00035
Pubmed ID
Authors

Katrin Zlabinger, Dominika Lukovic, Rayyan Hemetsberger, Alfred Gugerell, Johannes Winkler, Ljubica Mandic, Denise Traxler, Andreas Spannbauer, Susanne Wolbank, Gerald Zanoni, Christoph Kaun, Aniko Posa, Andrea Gyenes, Zsolt Petrasi, Örs Petnehazy, Imre Repa, Renate Hofer-Warbinek, Rainer de Martin, Florian Gruber, Silvia Charwat, Kurt Huber, Noemi Pavo, Imre J. Pavo, Noemi Nyolczas, Dara L. Kraitchman, Mariann Gyöngyösi

Abstract

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. 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. 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. 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.

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Mendeley readers

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The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 23%
Student > Doctoral Student 3 14%
Student > Ph. D. Student 3 14%
Other 2 9%
Professor 1 5%
Other 3 14%
Unknown 5 23%
Readers by discipline Count As %
Medicine and Dentistry 5 23%
Biochemistry, Genetics and Molecular Biology 4 18%
Pharmacology, Toxicology and Pharmaceutical Science 2 9%
Agricultural and Biological Sciences 1 5%
Psychology 1 5%
Other 3 14%
Unknown 6 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 April 2018.
All research outputs
#18,596,650
of 23,035,022 outputs
Outputs from Frontiers in Bioengineering and Biotechnology
#3,445
of 6,726 outputs
Outputs of similar age
#255,658
of 329,119 outputs
Outputs of similar age from Frontiers in Bioengineering and Biotechnology
#35
of 48 outputs
Altmetric has tracked 23,035,022 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,726 research outputs from this source. They receive a mean Attention Score of 3.4. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
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We're also able to compare this research output to 48 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.