Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia

Autores
Olea, Fernanda Daniela; Locatelli, Paola; Hnatiuk, Anna; De Lorenzi, Andrea; Valdivieso, León; Rocha, Estefanía; Ramirez, Rodrigo Julio; Laguens, Rubén; Crottogini, Alberto José
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objectives: Critical limb ischemia complicates peripheral artery disease leading to tissue damage and amputation. We hypothesized that modifying adipose stromal cells (ASCs) to overexpress human vascular endothelial growth factor 165 (VEGF) would limit ischemic muscle damage to a larger extent than nonmodified ASCs. Approach and Results: Rabbits with critical hindlimb ischemia were injected with allogeneic abdominal fat-derived ASCs transfected with plasmid-VEGF165 (ASCs-VEGF; n=10). Additional rabbits received nontransfected ASCs (ASCs; n=10) or vehicle (placebo; n=10). One month later, ASCs-VEGF rabbits exhibited significantly higher density of angiographically visible collaterals and capillaries versus placebo (both P<0.05) but not versus ASCs (both P=NS). Arteriolar density, however, was increased in both ASCs and ASCs-VEGF groups (both P<0.05 versus placebo). ASCs-VEGF and ASCs showed comparable post-treatment improvements in Doppler-assessed peak systolic velocity, blood pressure ratio, and resistance index. Ischemic lesions were found in 40% of the muscle samples in the placebo group, 19% in the ASCs-VEGF group, and 17% in the ASCs groups (both P<0.05 versus placebo, Fisher test). Conclusions: In a rabbit model of critical limb ischemia, intramuscular injection of ASCs genetically modified to overexpress VEGF increase angiographically visible collaterals and capillary density. However, both modified and nonmodified ASCs increase arteriolar density to a similar extent and afford equal protection against ischemia-induced muscle lesions. These results indicate that modifying ASCs to overexpress VEGF does not enhance the protective effect of ASCs, and that arteriolar proliferation plays a pivotal role in limiting the irreversible tissue damage of critical limb ischemia.
Fil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Hnatiuk, Anna. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: De Lorenzi, Andrea. Fundación Favaloro; Argentina
Fil: Valdivieso, León. Fundación Favaloro; Argentina
Fil: Rocha, Estefanía. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Ramirez, Rodrigo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Laguens, Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Crottogini, Alberto José. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Adult Somatic Stem Cells
Angiogenesis Effect
Vascular Endothelial Growth Factor A
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:11336/37960
Acceder
id CONICETDig_aaa6e8e29e0b8c011123886325065284
oai_identifier_str oai:ri.conicet.gov.ar:11336/37960
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemiaOlea, Fernanda DanielaLocatelli, PaolaHnatiuk, AnnaDe Lorenzi, AndreaValdivieso, LeónRocha, EstefaníaRamirez, Rodrigo JulioLaguens, RubénCrottogini, Alberto JoséAdult Somatic Stem CellsAngiogenesis EffectVascular Endothelial Growth Factor Ahttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Objectives: Critical limb ischemia complicates peripheral artery disease leading to tissue damage and amputation. We hypothesized that modifying adipose stromal cells (ASCs) to overexpress human vascular endothelial growth factor 165 (VEGF) would limit ischemic muscle damage to a larger extent than nonmodified ASCs. Approach and Results: Rabbits with critical hindlimb ischemia were injected with allogeneic abdominal fat-derived ASCs transfected with plasmid-VEGF165 (ASCs-VEGF; n=10). Additional rabbits received nontransfected ASCs (ASCs; n=10) or vehicle (placebo; n=10). One month later, ASCs-VEGF rabbits exhibited significantly higher density of angiographically visible collaterals and capillaries versus placebo (both P<0.05) but not versus ASCs (both P=NS). Arteriolar density, however, was increased in both ASCs and ASCs-VEGF groups (both P<0.05 versus placebo). ASCs-VEGF and ASCs showed comparable post-treatment improvements in Doppler-assessed peak systolic velocity, blood pressure ratio, and resistance index. Ischemic lesions were found in 40% of the muscle samples in the placebo group, 19% in the ASCs-VEGF group, and 17% in the ASCs groups (both P<0.05 versus placebo, Fisher test). Conclusions: In a rabbit model of critical limb ischemia, intramuscular injection of ASCs genetically modified to overexpress VEGF increase angiographically visible collaterals and capillary density. However, both modified and nonmodified ASCs increase arteriolar density to a similar extent and afford equal protection against ischemia-induced muscle lesions. These results indicate that modifying ASCs to overexpress VEGF does not enhance the protective effect of ASCs, and that arteriolar proliferation plays a pivotal role in limiting the irreversible tissue damage of critical limb ischemia.Fil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Hnatiuk, Anna. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: De Lorenzi, Andrea. Fundación Favaloro; ArgentinaFil: Valdivieso, León. Fundación Favaloro; ArgentinaFil: Rocha, Estefanía. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Ramirez, Rodrigo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Laguens, Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Crottogini, Alberto José. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaLippincott Williams2015-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/37960Olea, Fernanda Daniela; Locatelli, Paola; Hnatiuk, Anna; De Lorenzi, Andrea; Valdivieso, León; et al.; Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia; Lippincott Williams; Arteriosclerosis, Thrombosis, and Vascular Biology; 35; 1; 1-2015; 184-1881079-5642CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1161/ATVBAHA.114.304348info:eu-repo/semantics/altIdentifier/url/http://atvb.ahajournals.org/content/35/1/184info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:39Zoai:ri.conicet.gov.ar:11336/37960instacron: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:34982025-09-03 09:59:39.407CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia
title Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia
spellingShingle Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia
Olea, Fernanda Daniela
Adult Somatic Stem Cells
Angiogenesis Effect
Vascular Endothelial Growth Factor A
title_short Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia
title_full Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia
title_fullStr Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia
title_full_unstemmed Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia
title_sort Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia
dc.creator.none.fl_str_mv Olea, Fernanda Daniela
Locatelli, Paola
Hnatiuk, Anna
De Lorenzi, Andrea
Valdivieso, León
Rocha, Estefanía
Ramirez, Rodrigo Julio
Laguens, Rubén
Crottogini, Alberto José
author Olea, Fernanda Daniela
author_facet Olea, Fernanda Daniela
Locatelli, Paola
Hnatiuk, Anna
De Lorenzi, Andrea
Valdivieso, León
Rocha, Estefanía
Ramirez, Rodrigo Julio
Laguens, Rubén
Crottogini, Alberto José
author_role author
author2 Locatelli, Paola
Hnatiuk, Anna
De Lorenzi, Andrea
Valdivieso, León
Rocha, Estefanía
Ramirez, Rodrigo Julio
Laguens, Rubén
Crottogini, Alberto José
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Adult Somatic Stem Cells
Angiogenesis Effect
Vascular Endothelial Growth Factor A
topic Adult Somatic Stem Cells
Angiogenesis Effect
Vascular Endothelial Growth Factor A
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objectives: Critical limb ischemia complicates peripheral artery disease leading to tissue damage and amputation. We hypothesized that modifying adipose stromal cells (ASCs) to overexpress human vascular endothelial growth factor 165 (VEGF) would limit ischemic muscle damage to a larger extent than nonmodified ASCs. Approach and Results: Rabbits with critical hindlimb ischemia were injected with allogeneic abdominal fat-derived ASCs transfected with plasmid-VEGF165 (ASCs-VEGF; n=10). Additional rabbits received nontransfected ASCs (ASCs; n=10) or vehicle (placebo; n=10). One month later, ASCs-VEGF rabbits exhibited significantly higher density of angiographically visible collaterals and capillaries versus placebo (both P<0.05) but not versus ASCs (both P=NS). Arteriolar density, however, was increased in both ASCs and ASCs-VEGF groups (both P<0.05 versus placebo). ASCs-VEGF and ASCs showed comparable post-treatment improvements in Doppler-assessed peak systolic velocity, blood pressure ratio, and resistance index. Ischemic lesions were found in 40% of the muscle samples in the placebo group, 19% in the ASCs-VEGF group, and 17% in the ASCs groups (both P<0.05 versus placebo, Fisher test). Conclusions: In a rabbit model of critical limb ischemia, intramuscular injection of ASCs genetically modified to overexpress VEGF increase angiographically visible collaterals and capillary density. However, both modified and nonmodified ASCs increase arteriolar density to a similar extent and afford equal protection against ischemia-induced muscle lesions. These results indicate that modifying ASCs to overexpress VEGF does not enhance the protective effect of ASCs, and that arteriolar proliferation plays a pivotal role in limiting the irreversible tissue damage of critical limb ischemia.
Fil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Hnatiuk, Anna. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: De Lorenzi, Andrea. Fundación Favaloro; Argentina
Fil: Valdivieso, León. Fundación Favaloro; Argentina
Fil: Rocha, Estefanía. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Ramirez, Rodrigo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Laguens, Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Crottogini, Alberto José. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Objectives: Critical limb ischemia complicates peripheral artery disease leading to tissue damage and amputation. We hypothesized that modifying adipose stromal cells (ASCs) to overexpress human vascular endothelial growth factor 165 (VEGF) would limit ischemic muscle damage to a larger extent than nonmodified ASCs. Approach and Results: Rabbits with critical hindlimb ischemia were injected with allogeneic abdominal fat-derived ASCs transfected with plasmid-VEGF165 (ASCs-VEGF; n=10). Additional rabbits received nontransfected ASCs (ASCs; n=10) or vehicle (placebo; n=10). One month later, ASCs-VEGF rabbits exhibited significantly higher density of angiographically visible collaterals and capillaries versus placebo (both P<0.05) but not versus ASCs (both P=NS). Arteriolar density, however, was increased in both ASCs and ASCs-VEGF groups (both P<0.05 versus placebo). ASCs-VEGF and ASCs showed comparable post-treatment improvements in Doppler-assessed peak systolic velocity, blood pressure ratio, and resistance index. Ischemic lesions were found in 40% of the muscle samples in the placebo group, 19% in the ASCs-VEGF group, and 17% in the ASCs groups (both P<0.05 versus placebo, Fisher test). Conclusions: In a rabbit model of critical limb ischemia, intramuscular injection of ASCs genetically modified to overexpress VEGF increase angiographically visible collaterals and capillary density. However, both modified and nonmodified ASCs increase arteriolar density to a similar extent and afford equal protection against ischemia-induced muscle lesions. These results indicate that modifying ASCs to overexpress VEGF does not enhance the protective effect of ASCs, and that arteriolar proliferation plays a pivotal role in limiting the irreversible tissue damage of critical limb ischemia.
publishDate 2015
dc.date.none.fl_str_mv 2015-01
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/11336/37960
Olea, Fernanda Daniela; Locatelli, Paola; Hnatiuk, Anna; De Lorenzi, Andrea; Valdivieso, León; et al.; Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia; Lippincott Williams; Arteriosclerosis, Thrombosis, and Vascular Biology; 35; 1; 1-2015; 184-188
1079-5642
CONICET Digital
CONICET
url http://hdl.handle.net/11336/37960
identifier_str_mv Olea, Fernanda Daniela; Locatelli, Paola; Hnatiuk, Anna; De Lorenzi, Andrea; Valdivieso, León; et al.; Vascular endothelial growth factor overexpression does not enhance adipose stromal cell-induced protection on muscle damage in critical limb ischemia; Lippincott Williams; Arteriosclerosis, Thrombosis, and Vascular Biology; 35; 1; 1-2015; 184-188
1079-5642
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1161/ATVBAHA.114.304348
info:eu-repo/semantics/altIdentifier/url/http://atvb.ahajournals.org/content/35/1/184
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
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
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
_version_ 1842269593420169216
score 13.13397

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