Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction

Gene Therapy
Paola LocatelliAlberto Crottogini

Abstract

Mesenchymal stromal cells (MSCs) are cardioprotective in acute myocardial infarction (AMI). Besides, we have shown that intramyocardial injection of plasmid-VEGF(165) (pVEGF) in ovine AMI reduces infarct size and improves left ventricular (LV) function. We thus hypothesized that MSCs overexpressing VEGF(165) (MSCs-pVEGF) would afford greater cardioprotection than non-modified MSCs or pVEGF alone. Sheep underwent an anteroapical AMI and, 1 week later, received intramyocardial MSCs-pVEGF in the infarct border. One month post treatment, infarct size (magnetic resonance) decreased by 31% vs pre-treatment. Of note, myocardial salvage occurred predominantly at the subendocardium, the myocardial region displaying the largest contribution to systolic performance. Consistently, LV ejection fraction recovered to almost its baseline value because of marked decrease in end-systolic volume. None of these effects were observed in sheep receiving non-transfected MSCs or pVEGF. Although myocardial retention of MSCs decreased steeply over time, the treatment induced significant capillary and arteriolar proliferation, which reduced subendocardial fibrosis. We conclude that in ovine AMI, allogeneic VEGF-overexpressing MSCs induce subendocardial m...Continue Reading

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Citations

Mar 8, 2016·IUBMB Life·Sally M ShalabyDalia M Abd El Motteleb
Aug 3, 2018·Current Drug Targets·Paola LocatelliMariano Nicolás Belaich
Jan 10, 2019·Stem Cells International·Zhi ChenWei Eric Wang
Sep 26, 2020·Frontiers in Cell and Developmental Biology·Patricia Kauanna Fonseca DamascenoMilena Botelho Pereira Soares
Oct 9, 2020·Growth Factors·Maria Rosaria De PascaleClaudio Napoli
Nov 24, 2019·Seminars in Cell & Developmental Biology·Jason S RockelSowmya Viswanathan
Mar 5, 2021·Stem Cells Translational Medicine·Raquel Cruz-SamperioAdam Perriman

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