Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells

Autores
Mena, Hebe Agustina; Lokajczyk, Anna; Dizier, Blandine; Strier, Sergio E.; Voto, Liliana S.; Boisson Vidal, Catherine; Schattner, Mirta Ana; Negrotto, Soledad
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: Acidosis is present in several pathological conditions where vasculogenesis takes place including ischemia, tumor growth and wound healing. We have previously demonstrated that acidosis induces human CD34+ cell apoptosis. Considering that endothelial colony-forming cells (ECFC) are a subpopulation of CD34+ cells and key players in vasculogenesis, in the present study we investigated the effect of acidosis on the survival and functionality of ECFC. Approach and results: Endothelial colony-forming cells obtained by differentiation of human cord blood CD34+ cells in endothelial growth medium-2 for 14–21 days were exposed at pH 7.4, 7.0 or 6.6. We found that acidosis failed to induce ECFC apoptosis and, although an early reduction in proliferation, chemotaxis, wound healing and capillary-like tubule formation was observed, once the medium pH was restored to 7.4, ECFC proliferation and tubulogenesis were augmented. Stromal cell derived factor-1 (SDF1)-driven migration and chemokine receptor type 4 surface expression were also increased. The maximal proangiogenic effect exerted by acidic preconditioning was observed after 6 h at pH 6.6. Furthermore, preconditioned ECFC showed an increased ability to promote tissue revascularization in a murine model of hind limb ischemia. Immunoblotting assays showed that acidosis activated AKT and ERK1/2 and inhibited p38 pathways. Proliferation rises triggered by acidic preconditioning were no longer observed after AKT or ERK1/2 inhibition, whereas p38 suppression not only mimicked but also potentiated the effect of acidosis on ECFC tubule formation abilities. Conclusions: These results demonstrate that acidic preconditioning greatly increases ECFC-mediated angiogenesis in vitro including ECFC proliferation, tubulogenesis and SDF1-driven chemotaxis and is a positive regulator of microvessel formation in vivo.
Fil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lokajczyk, Anna. Université Paris Descartes; Francia. Inserm; Francia
Fil: Dizier, Blandine. Inserm; Francia
Fil: Strier, Sergio E.. Ciudad Autónoma de Buenos Aires. Hospital "Bernardino Rivadavia"; Argentina
Fil: Voto, Liliana S.. Ciudad Autónoma de Buenos Aires. Hospital "Juan A. Fernández"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Boisson Vidal, Catherine. Université Paris Descartes; Francia. Inserm; Francia
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
Endothelial Colony-Forming Cells
Vasculogenesis
Acidic Preconditioning
Acidosis
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:11336/29417
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/29417
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cellsMena, Hebe AgustinaLokajczyk, AnnaDizier, BlandineStrier, Sergio E.Voto, Liliana S.Boisson Vidal, CatherineSchattner, Mirta AnaNegrotto, SoledadEndothelial Colony-Forming CellsVasculogenesisAcidic PreconditioningAcidosishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Objective: Acidosis is present in several pathological conditions where vasculogenesis takes place including ischemia, tumor growth and wound healing. We have previously demonstrated that acidosis induces human CD34+ cell apoptosis. Considering that endothelial colony-forming cells (ECFC) are a subpopulation of CD34+ cells and key players in vasculogenesis, in the present study we investigated the effect of acidosis on the survival and functionality of ECFC. Approach and results: Endothelial colony-forming cells obtained by differentiation of human cord blood CD34+ cells in endothelial growth medium-2 for 14–21 days were exposed at pH 7.4, 7.0 or 6.6. We found that acidosis failed to induce ECFC apoptosis and, although an early reduction in proliferation, chemotaxis, wound healing and capillary-like tubule formation was observed, once the medium pH was restored to 7.4, ECFC proliferation and tubulogenesis were augmented. Stromal cell derived factor-1 (SDF1)-driven migration and chemokine receptor type 4 surface expression were also increased. The maximal proangiogenic effect exerted by acidic preconditioning was observed after 6 h at pH 6.6. Furthermore, preconditioned ECFC showed an increased ability to promote tissue revascularization in a murine model of hind limb ischemia. Immunoblotting assays showed that acidosis activated AKT and ERK1/2 and inhibited p38 pathways. Proliferation rises triggered by acidic preconditioning were no longer observed after AKT or ERK1/2 inhibition, whereas p38 suppression not only mimicked but also potentiated the effect of acidosis on ECFC tubule formation abilities. Conclusions: These results demonstrate that acidic preconditioning greatly increases ECFC-mediated angiogenesis in vitro including ECFC proliferation, tubulogenesis and SDF1-driven chemotaxis and is a positive regulator of microvessel formation in vivo.Fil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Lokajczyk, Anna. Université Paris Descartes; Francia. Inserm; FranciaFil: Dizier, Blandine. Inserm; FranciaFil: Strier, Sergio E.. Ciudad Autónoma de Buenos Aires. Hospital "Bernardino Rivadavia"; ArgentinaFil: Voto, Liliana S.. Ciudad Autónoma de Buenos Aires. Hospital "Juan A. Fernández"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Boisson Vidal, Catherine. Université Paris Descartes; Francia. Inserm; FranciaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaSpringer2014-05info: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/11336/29417Mena, Hebe Agustina; Lokajczyk, Anna; Dizier, Blandine; Strier, Sergio E.; Voto, Liliana S.; et al.; Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells; Springer; Angiogenesis; 17; 4; 5-2014; 867-8790969-69701573-7209CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s10456-014-9434-5info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s10456-014-9434-5info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:45Zoai:ri.conicet.gov.ar:11336/29417instacron: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 09:56:46.036CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells
title Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells
spellingShingle Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells
Mena, Hebe Agustina
Endothelial Colony-Forming Cells
Vasculogenesis
Acidic Preconditioning
Acidosis
title_short Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells
title_full Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells
title_fullStr Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells
title_full_unstemmed Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells
title_sort Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells
dc.creator.none.fl_str_mv Mena, Hebe Agustina
Lokajczyk, Anna
Dizier, Blandine
Strier, Sergio E.
Voto, Liliana S.
Boisson Vidal, Catherine
Schattner, Mirta Ana
Negrotto, Soledad
author Mena, Hebe Agustina
author_facet Mena, Hebe Agustina
Lokajczyk, Anna
Dizier, Blandine
Strier, Sergio E.
Voto, Liliana S.
Boisson Vidal, Catherine
Schattner, Mirta Ana
Negrotto, Soledad
author_role author
author2 Lokajczyk, Anna
Dizier, Blandine
Strier, Sergio E.
Voto, Liliana S.
Boisson Vidal, Catherine
Schattner, Mirta Ana
Negrotto, Soledad
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Endothelial Colony-Forming Cells
Vasculogenesis
Acidic Preconditioning
Acidosis
topic Endothelial Colony-Forming Cells
Vasculogenesis
Acidic Preconditioning
Acidosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: Acidosis is present in several pathological conditions where vasculogenesis takes place including ischemia, tumor growth and wound healing. We have previously demonstrated that acidosis induces human CD34+ cell apoptosis. Considering that endothelial colony-forming cells (ECFC) are a subpopulation of CD34+ cells and key players in vasculogenesis, in the present study we investigated the effect of acidosis on the survival and functionality of ECFC. Approach and results: Endothelial colony-forming cells obtained by differentiation of human cord blood CD34+ cells in endothelial growth medium-2 for 14–21 days were exposed at pH 7.4, 7.0 or 6.6. We found that acidosis failed to induce ECFC apoptosis and, although an early reduction in proliferation, chemotaxis, wound healing and capillary-like tubule formation was observed, once the medium pH was restored to 7.4, ECFC proliferation and tubulogenesis were augmented. Stromal cell derived factor-1 (SDF1)-driven migration and chemokine receptor type 4 surface expression were also increased. The maximal proangiogenic effect exerted by acidic preconditioning was observed after 6 h at pH 6.6. Furthermore, preconditioned ECFC showed an increased ability to promote tissue revascularization in a murine model of hind limb ischemia. Immunoblotting assays showed that acidosis activated AKT and ERK1/2 and inhibited p38 pathways. Proliferation rises triggered by acidic preconditioning were no longer observed after AKT or ERK1/2 inhibition, whereas p38 suppression not only mimicked but also potentiated the effect of acidosis on ECFC tubule formation abilities. Conclusions: These results demonstrate that acidic preconditioning greatly increases ECFC-mediated angiogenesis in vitro including ECFC proliferation, tubulogenesis and SDF1-driven chemotaxis and is a positive regulator of microvessel formation in vivo.
Fil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lokajczyk, Anna. Université Paris Descartes; Francia. Inserm; Francia
Fil: Dizier, Blandine. Inserm; Francia
Fil: Strier, Sergio E.. Ciudad Autónoma de Buenos Aires. Hospital "Bernardino Rivadavia"; Argentina
Fil: Voto, Liliana S.. Ciudad Autónoma de Buenos Aires. Hospital "Juan A. Fernández"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Boisson Vidal, Catherine. Université Paris Descartes; Francia. Inserm; Francia
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Objective: Acidosis is present in several pathological conditions where vasculogenesis takes place including ischemia, tumor growth and wound healing. We have previously demonstrated that acidosis induces human CD34+ cell apoptosis. Considering that endothelial colony-forming cells (ECFC) are a subpopulation of CD34+ cells and key players in vasculogenesis, in the present study we investigated the effect of acidosis on the survival and functionality of ECFC. Approach and results: Endothelial colony-forming cells obtained by differentiation of human cord blood CD34+ cells in endothelial growth medium-2 for 14–21 days were exposed at pH 7.4, 7.0 or 6.6. We found that acidosis failed to induce ECFC apoptosis and, although an early reduction in proliferation, chemotaxis, wound healing and capillary-like tubule formation was observed, once the medium pH was restored to 7.4, ECFC proliferation and tubulogenesis were augmented. Stromal cell derived factor-1 (SDF1)-driven migration and chemokine receptor type 4 surface expression were also increased. The maximal proangiogenic effect exerted by acidic preconditioning was observed after 6 h at pH 6.6. Furthermore, preconditioned ECFC showed an increased ability to promote tissue revascularization in a murine model of hind limb ischemia. Immunoblotting assays showed that acidosis activated AKT and ERK1/2 and inhibited p38 pathways. Proliferation rises triggered by acidic preconditioning were no longer observed after AKT or ERK1/2 inhibition, whereas p38 suppression not only mimicked but also potentiated the effect of acidosis on ECFC tubule formation abilities. Conclusions: These results demonstrate that acidic preconditioning greatly increases ECFC-mediated angiogenesis in vitro including ECFC proliferation, tubulogenesis and SDF1-driven chemotaxis and is a positive regulator of microvessel formation in vivo.
publishDate 2014
dc.date.none.fl_str_mv 2014-05
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/11336/29417
Mena, Hebe Agustina; Lokajczyk, Anna; Dizier, Blandine; Strier, Sergio E.; Voto, Liliana S.; et al.; Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells; Springer; Angiogenesis; 17; 4; 5-2014; 867-879
0969-6970
1573-7209
CONICET Digital
CONICET
url http://hdl.handle.net/11336/29417
identifier_str_mv Mena, Hebe Agustina; Lokajczyk, Anna; Dizier, Blandine; Strier, Sergio E.; Voto, Liliana S.; et al.; Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells; Springer; Angiogenesis; 17; 4; 5-2014; 867-879
0969-6970
1573-7209
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s10456-014-9434-5
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s10456-014-9434-5
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 Springer
publisher.none.fl_str_mv Springer
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 13.13397

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