A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus

Autores
Bolontrade, Marcela Fabiana; Sganga, Leonardo; Piaggio, Eduardo; Viale, Diego Luis; Sorrentino, Miguel A.; Robinson, Anibal; Sevlever, Gustavo; García, Mariana Gabriela; Mazzolini Rizzo, Guillermo Daniel; Podhajcer, Osvaldo Luis
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The homing properties of mesenchymal stromal c'ells (MSCs) toward tumors turn them into attractive tools for combining cell and gene therapy. The aim of this study was to select in a feasible way a human bone marrowderived MSC subpopulation that might exhibit a selective ability to target the tumor mass. Using differential in vitro adhesive capacities during cells isolation, we selected a specific MSC subpopulation (termed MO-MSCs) that exhibited enhanced multipotent capacity and increased cell surface expression of specific integrins (integrins a2, a3, and a5), which correlated with an enhanced MO-MSCs adhesiveness toward their specific ligands. Moreover, MO-MSCs exhibited a higher migration toward conditioned media from different cancer cell lines and fresh human breast cancer samples in the presence or not of a human microendothelium monolayer. Further in vivo studies demonstrated increased tumor homing of MO-MSCs toward established 578T and MD-MBA-231 breast cancer and A375N melanoma tumor xenografts. Tumor penetration by MO-MSCs was highly dependent on metallopeptidases production as it was inhibited by the specific inhibitor 1,10 phenantroline. Finally, systemically administered MO-MSCs preloaded with an oncolytic adenovirus significantly inhibited tumor growth in mice harboring established A375N melanomas, overcoming the natural resistance of the tumor to in situ administration of the oncolytic adenovirus. In summary, this work characterizes a novel MSC subpopulation with increased tumor homing capacity that can be used to transport therapeutic compounds.
Fil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Sganga, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Piaggio, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Viale, Diego Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Sorrentino, Miguel A.. Ministerio de Defensa. Perfectura Naval Argentina. Departamento Científico; Argentina
Fil: Robinson, Anibal. Ministerio de Defensa. Perfectura Naval Argentina. Departamento Científico; Argentina
Fil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: García, Mariana Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Materia
Mesenchimal Stromal Cells
Melanoma
Gene Therapy
CRAds
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:11336/137940
Acceder
id CONICETDig_afeced3a954194de197294c667ecefba
oai_identifier_str oai:ri.conicet.gov.ar:11336/137940
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirusBolontrade, Marcela FabianaSganga, LeonardoPiaggio, EduardoViale, Diego LuisSorrentino, Miguel A.Robinson, AnibalSevlever, GustavoGarcía, Mariana GabrielaMazzolini Rizzo, Guillermo DanielPodhajcer, Osvaldo LuisMesenchimal Stromal CellsMelanomaGene TherapyCRAdshttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3The homing properties of mesenchymal stromal c'ells (MSCs) toward tumors turn them into attractive tools for combining cell and gene therapy. The aim of this study was to select in a feasible way a human bone marrowderived MSC subpopulation that might exhibit a selective ability to target the tumor mass. Using differential in vitro adhesive capacities during cells isolation, we selected a specific MSC subpopulation (termed MO-MSCs) that exhibited enhanced multipotent capacity and increased cell surface expression of specific integrins (integrins a2, a3, and a5), which correlated with an enhanced MO-MSCs adhesiveness toward their specific ligands. Moreover, MO-MSCs exhibited a higher migration toward conditioned media from different cancer cell lines and fresh human breast cancer samples in the presence or not of a human microendothelium monolayer. Further in vivo studies demonstrated increased tumor homing of MO-MSCs toward established 578T and MD-MBA-231 breast cancer and A375N melanoma tumor xenografts. Tumor penetration by MO-MSCs was highly dependent on metallopeptidases production as it was inhibited by the specific inhibitor 1,10 phenantroline. Finally, systemically administered MO-MSCs preloaded with an oncolytic adenovirus significantly inhibited tumor growth in mice harboring established A375N melanomas, overcoming the natural resistance of the tumor to in situ administration of the oncolytic adenovirus. In summary, this work characterizes a novel MSC subpopulation with increased tumor homing capacity that can be used to transport therapeutic compounds.Fil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Sganga, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Piaggio, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Viale, Diego Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Sorrentino, Miguel A.. Ministerio de Defensa. Perfectura Naval Argentina. Departamento Científico; ArgentinaFil: Robinson, Anibal. Ministerio de Defensa. Perfectura Naval Argentina. Departamento Científico; ArgentinaFil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: García, Mariana Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; ArgentinaFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaMary Ann Liebert2012-05-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/137940Bolontrade, Marcela Fabiana; Sganga, Leonardo; Piaggio, Eduardo; Viale, Diego Luis; Sorrentino, Miguel A.; et al.; A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus; Mary Ann Liebert; Stem Cells And Development; 21; 14; 14-5-2012; 2689-27021547-32871557-8534CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.liebertpub.com/doi/10.1089/scd.2011.0643info:eu-repo/semantics/altIdentifier/doi/10.1089/scd.2011.0643info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:59Zoai:ri.conicet.gov.ar:11336/137940instacron: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 09:52:00.284CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus
title A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus
spellingShingle A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus
Bolontrade, Marcela Fabiana
Mesenchimal Stromal Cells
Melanoma
Gene Therapy
CRAds
title_short A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus
title_full A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus
title_fullStr A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus
title_full_unstemmed A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus
title_sort A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus
dc.creator.none.fl_str_mv Bolontrade, Marcela Fabiana
Sganga, Leonardo
Piaggio, Eduardo
Viale, Diego Luis
Sorrentino, Miguel A.
Robinson, Anibal
Sevlever, Gustavo
García, Mariana Gabriela
Mazzolini Rizzo, Guillermo Daniel
Podhajcer, Osvaldo Luis
author Bolontrade, Marcela Fabiana
author_facet Bolontrade, Marcela Fabiana
Sganga, Leonardo
Piaggio, Eduardo
Viale, Diego Luis
Sorrentino, Miguel A.
Robinson, Anibal
Sevlever, Gustavo
García, Mariana Gabriela
Mazzolini Rizzo, Guillermo Daniel
Podhajcer, Osvaldo Luis
author_role author
author2 Sganga, Leonardo
Piaggio, Eduardo
Viale, Diego Luis
Sorrentino, Miguel A.
Robinson, Anibal
Sevlever, Gustavo
García, Mariana Gabriela
Mazzolini Rizzo, Guillermo Daniel
Podhajcer, Osvaldo Luis
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mesenchimal Stromal Cells
Melanoma
Gene Therapy
CRAds
topic Mesenchimal Stromal Cells
Melanoma
Gene Therapy
CRAds
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The homing properties of mesenchymal stromal c'ells (MSCs) toward tumors turn them into attractive tools for combining cell and gene therapy. The aim of this study was to select in a feasible way a human bone marrowderived MSC subpopulation that might exhibit a selective ability to target the tumor mass. Using differential in vitro adhesive capacities during cells isolation, we selected a specific MSC subpopulation (termed MO-MSCs) that exhibited enhanced multipotent capacity and increased cell surface expression of specific integrins (integrins a2, a3, and a5), which correlated with an enhanced MO-MSCs adhesiveness toward their specific ligands. Moreover, MO-MSCs exhibited a higher migration toward conditioned media from different cancer cell lines and fresh human breast cancer samples in the presence or not of a human microendothelium monolayer. Further in vivo studies demonstrated increased tumor homing of MO-MSCs toward established 578T and MD-MBA-231 breast cancer and A375N melanoma tumor xenografts. Tumor penetration by MO-MSCs was highly dependent on metallopeptidases production as it was inhibited by the specific inhibitor 1,10 phenantroline. Finally, systemically administered MO-MSCs preloaded with an oncolytic adenovirus significantly inhibited tumor growth in mice harboring established A375N melanomas, overcoming the natural resistance of the tumor to in situ administration of the oncolytic adenovirus. In summary, this work characterizes a novel MSC subpopulation with increased tumor homing capacity that can be used to transport therapeutic compounds.
Fil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Sganga, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Piaggio, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Viale, Diego Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Sorrentino, Miguel A.. Ministerio de Defensa. Perfectura Naval Argentina. Departamento Científico; Argentina
Fil: Robinson, Anibal. Ministerio de Defensa. Perfectura Naval Argentina. Departamento Científico; Argentina
Fil: Sevlever, Gustavo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: García, Mariana Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina
Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
description The homing properties of mesenchymal stromal c'ells (MSCs) toward tumors turn them into attractive tools for combining cell and gene therapy. The aim of this study was to select in a feasible way a human bone marrowderived MSC subpopulation that might exhibit a selective ability to target the tumor mass. Using differential in vitro adhesive capacities during cells isolation, we selected a specific MSC subpopulation (termed MO-MSCs) that exhibited enhanced multipotent capacity and increased cell surface expression of specific integrins (integrins a2, a3, and a5), which correlated with an enhanced MO-MSCs adhesiveness toward their specific ligands. Moreover, MO-MSCs exhibited a higher migration toward conditioned media from different cancer cell lines and fresh human breast cancer samples in the presence or not of a human microendothelium monolayer. Further in vivo studies demonstrated increased tumor homing of MO-MSCs toward established 578T and MD-MBA-231 breast cancer and A375N melanoma tumor xenografts. Tumor penetration by MO-MSCs was highly dependent on metallopeptidases production as it was inhibited by the specific inhibitor 1,10 phenantroline. Finally, systemically administered MO-MSCs preloaded with an oncolytic adenovirus significantly inhibited tumor growth in mice harboring established A375N melanomas, overcoming the natural resistance of the tumor to in situ administration of the oncolytic adenovirus. In summary, this work characterizes a novel MSC subpopulation with increased tumor homing capacity that can be used to transport therapeutic compounds.
publishDate 2012
dc.date.none.fl_str_mv 2012-05-14
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/11336/137940
Bolontrade, Marcela Fabiana; Sganga, Leonardo; Piaggio, Eduardo; Viale, Diego Luis; Sorrentino, Miguel A.; et al.; A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus; Mary Ann Liebert; Stem Cells And Development; 21; 14; 14-5-2012; 2689-2702
1547-3287
1557-8534
CONICET Digital
CONICET
url http://hdl.handle.net/11336/137940
identifier_str_mv Bolontrade, Marcela Fabiana; Sganga, Leonardo; Piaggio, Eduardo; Viale, Diego Luis; Sorrentino, Miguel A.; et al.; A specific subpopulation of mesenchymal stromal cell carriers overrides melanoma resistance to an oncolytic adenovirus; Mary Ann Liebert; Stem Cells And Development; 21; 14; 14-5-2012; 2689-2702
1547-3287
1557-8534
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.liebertpub.com/doi/10.1089/scd.2011.0643
info:eu-repo/semantics/altIdentifier/doi/10.1089/scd.2011.0643
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
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Mary Ann Liebert
publisher.none.fl_str_mv Mary Ann Liebert
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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