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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/38588
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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 Técnicas2025-09-29T09:52:19Zoai: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:34982025-09-29 09:52:19.31CONICET 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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1844613605468667904 |
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13.070432 |