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Artículo

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

Locatelli, PaolaIcon ; Olea, Fernanda DanielaIcon ; Hnatiuk, Anna; De Lorenzi, Andrea; Cerda, Martín E.; Giménez, Carlos SebastiánIcon ; Sepúlveda, Diana ElizabethIcon ; Laguens, RubénIcon ; Crottogini, Alberto JoséIcon
Fecha de publicación: 06/2015
Editorial: Nature Publishing Group
Revista: Gene Therapy
ISSN: 0969-7128
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Tecnologías que involucran la manipulación de células, tejidos, órganos o todo el organismo; Fisiología

Resumen

Mesenchymal stromal cells (MSCs) are cardioprotective in acute myocardial infarction (AMI). Besides, we have shown that intramyocardial injection of plasmid-VEGF165 (pVEGF) in ovine AMI reduces infarct size and improves left ventricular (LV) function. We thus hypothesized that MSCs overexpressing VEGF165 (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 myocardium salvage through microvascular proliferation, reducing infarct size and improving LV function more than non-transfected MSCs or the naked plasmid. Importantly, the use of a plasmid rather than a virus allows for repeated treatments, likely needed in ischemic heart disease.
Palabras clave: Mesenchymal Stem Cells , Vegf , Acute Myocardial Infarction , Sheep
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
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URI: http://hdl.handle.net/11336/38588
URL: https://www.nature.com/articles/gt201528
DOI: http://dx.doi.org/10.1038/gt.2015.28
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Articulos(SEDE CENTRAL)
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Citación
Locatelli, Paola; Olea, Fernanda Daniela; Hnatiuk, Anna; De Lorenzi, Andrea; Cerda, Martín E.; et al.; Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction; Nature Publishing Group; Gene Therapy; 22; 6; 6-2015; 449-457
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