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

Autores
Locatelli, Paola; Olea, Fernanda Daniela; Hnatiuk, Anna; De Lorenzi, Andrea; Cerda, Martín E.; Giménez, Carlos Sebastián; Sepúlveda, Diana Elizabeth; Laguens, Rubén; Crottogini, Alberto José
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina
Fil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina
Fil: Hnatiuk, Anna. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina
Fil: De Lorenzi, Andrea. Universidad Favaloro; Argentina. Fundación Favaloro; Argentina
Fil: Cerda, Martín E.. Universidad Favaloro; Argentina. Fundación Favaloro; Argentina
Fil: Giménez, Carlos Sebastián. Fundación Favaloro; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sepúlveda, Diana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina
Fil: Laguens, Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina
Fil: Crottogini, Alberto José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina
Materia
Mesenchymal Stem Cells
Vegf
Acute Myocardial Infarction
Sheep
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/38588
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/38588
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarctionLocatelli, PaolaOlea, Fernanda DanielaHnatiuk, AnnaDe Lorenzi, AndreaCerda, Martín E.Giménez, Carlos SebastiánSepúlveda, Diana ElizabethLaguens, RubénCrottogini, Alberto JoséMesenchymal Stem CellsVegfAcute Myocardial InfarctionSheephttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Mesenchymal 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.Fil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; ArgentinaFil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; ArgentinaFil: Hnatiuk, Anna. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; ArgentinaFil: De Lorenzi, Andrea. Universidad Favaloro; Argentina. Fundación Favaloro; ArgentinaFil: Cerda, Martín E.. Universidad Favaloro; Argentina. Fundación Favaloro; ArgentinaFil: Giménez, Carlos Sebastián. Fundación Favaloro; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sepúlveda, Diana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; ArgentinaFil: Laguens, Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; ArgentinaFil: Crottogini, Alberto José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; ArgentinaNature Publishing Group2015-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38588Locatelli, 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; 449-4570969-7128CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/gt201528info:eu-repo/semantics/altIdentifier/doi/10.1038/gt.2015.28info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:21:43Zoai:ri.conicet.gov.ar:11336/38588instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:21:43.904CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction
title Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction
spellingShingle Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction
Locatelli, Paola
Mesenchymal Stem Cells
Vegf
Acute Myocardial Infarction
Sheep
title_short Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction
title_full Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction
title_fullStr Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction
title_full_unstemmed Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction
title_sort Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction
dc.creator.none.fl_str_mv Locatelli, Paola
Olea, Fernanda Daniela
Hnatiuk, Anna
De Lorenzi, Andrea
Cerda, Martín E.
Giménez, Carlos Sebastián
Sepúlveda, Diana Elizabeth
Laguens, Rubén
Crottogini, Alberto José
author Locatelli, Paola
author_facet Locatelli, Paola
Olea, Fernanda Daniela
Hnatiuk, Anna
De Lorenzi, Andrea
Cerda, Martín E.
Giménez, Carlos Sebastián
Sepúlveda, Diana Elizabeth
Laguens, Rubén
Crottogini, Alberto José
author_role author
author2 Olea, Fernanda Daniela
Hnatiuk, Anna
De Lorenzi, Andrea
Cerda, Martín E.
Giménez, Carlos Sebastián
Sepúlveda, Diana Elizabeth
Laguens, Rubén
Crottogini, Alberto José
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mesenchymal Stem Cells
Vegf
Acute Myocardial Infarction
Sheep
topic Mesenchymal Stem Cells
Vegf
Acute Myocardial Infarction
Sheep
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina
Fil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina
Fil: Hnatiuk, Anna. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina
Fil: De Lorenzi, Andrea. Universidad Favaloro; Argentina. Fundación Favaloro; Argentina
Fil: Cerda, Martín E.. Universidad Favaloro; Argentina. Fundación Favaloro; Argentina
Fil: Giménez, Carlos Sebastián. Fundación Favaloro; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sepúlveda, Diana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina
Fil: Laguens, Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina
Fil: Crottogini, Alberto José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Instituto de Investigación en Ciencias Básicas. Departamento de Ciencias Fisiológicas, Farmacológicas y Bioquímicas; Argentina
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/38588
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
0969-7128
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38588
identifier_str_mv 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
0969-7128
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/gt201528
info:eu-repo/semantics/altIdentifier/doi/10.1038/gt.2015.28
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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