Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice

Autores
Fiore, Esteban Juan; Bayo Fina, Juan Miguel; García, Mariana Gabriela; Malvicini, Mariana; Lloyd, Rodrigo; Piccioni, Flavia Valeria; Rizzo, Manglio Miguel; Peixoto, Estanislao; Sola, M. Beatriz; Atorrasagasti, María Catalina; Alaniz, Laura Daniela; Camilletti, María Andrea; Enguita, Mónica; Prieto, Jesús; Aquino, Jorge Benjamin; Mazzolini Rizzo, Guillermo Daniel
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Liver cirrhosis involves chronic wound healing and fibrotic processes. Mesenchymal stromal cells (MSCs) are multipotent adult progenitor cells that are used as vehicles of therapeutic genes. Insulin growth factor like-I (IGF-I) was shown to counteract liver fibrosis. We aimed at analyzing the effect of applying IGF-I overexpressing mouse bone marrow-derived MSCs on hepatic fibrosis. Fibrosis was induced by chronic thioacetamide application or bile duct ligation. MSCs engineered to produce green fluorescent protein (GFP) (AdGFP-MSCs) or IGF-I (AdIGF-I-MSCs) were applied systemically, and changes in collagen deposition and in the expression of key pro-fibrogenic and pro-regenerative genes/proteins were assessed. In addition, immunogenicity of transduced cells was analyzed. Liver fibrosis was further ameliorated after a single-dose application of AdIGF-I-MSCs when compared with AdGFP-MSCs and/or recombinant IGF-I treatments. Interestingly, an early and transitory upregulation in IGF-I and hepatocyte growth factor (HGF) mRNA expression was found in the liver of MSC-treated animals, which was more pronounced in AdIGF-I-MSCs condition. A reduction in hepatic stellate cell activation status was found after incubation with MSCs conditioned media. In addition, the AdIGF-I-MSCs cell-free supernatant induced the expression of IGF-I and HGF in primary cultured hepatocytes. From day 1 after transplantation, the proliferation marker proliferating cell nuclear antigen was upregulated in the liver of AdIGF-I-MSCs group, mainly in hepatocytes. MSCs were in vivo traced till day 14 after injection. In addition, multiple doses of Ad-IGF-I-MSCs likely suppressed antiviral immune response and it further reduced collagen deposition. Our results uncover early events that are likely involved in the anti-fibrogenic effect of genetically modified MSCs and overall would support the use of AdIGF-I-MSCs in treatment of liver fibrosis.
Fil: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Bayo Fina, Juan Miguel. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Malvicini, Mariana. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Lloyd, Rodrigo. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Piccioni, Flavia Valeria. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Rizzo, Manglio Miguel. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Peixoto, Estanislao. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Sola, M. Beatriz. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Atorrasagasti, María Catalina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Camilletti, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Enguita, Mónica. Centro de Investigación Médica Aplicada. Pamplona; España
Fil: Prieto, Jesús. Centro de Investigación Médica Aplicada. Pamplona; España
Fil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Materia
Mesenchymal Stem Cells
Insulin Growth Factor-Like 1
Hgf
Liver Regeneration
Tgf-1
Hepatic Stellate Cells
Cirrhosis
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:11336/36546
Acceder
id CONICETDig_3ff029625927f60269ace5c59e73c273
oai_identifier_str oai:ri.conicet.gov.ar:11336/36546
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in miceFiore, Esteban JuanBayo Fina, Juan MiguelGarcía, Mariana GabrielaMalvicini, MarianaLloyd, RodrigoPiccioni, Flavia ValeriaRizzo, Manglio MiguelPeixoto, EstanislaoSola, M. BeatrizAtorrasagasti, María CatalinaAlaniz, Laura DanielaCamilletti, María AndreaEnguita, MónicaPrieto, JesúsAquino, Jorge BenjaminMazzolini Rizzo, Guillermo DanielMesenchymal Stem CellsInsulin Growth Factor-Like 1HgfLiver RegenerationTgf-1Hepatic Stellate CellsCirrhosishttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Liver cirrhosis involves chronic wound healing and fibrotic processes. Mesenchymal stromal cells (MSCs) are multipotent adult progenitor cells that are used as vehicles of therapeutic genes. Insulin growth factor like-I (IGF-I) was shown to counteract liver fibrosis. We aimed at analyzing the effect of applying IGF-I overexpressing mouse bone marrow-derived MSCs on hepatic fibrosis. Fibrosis was induced by chronic thioacetamide application or bile duct ligation. MSCs engineered to produce green fluorescent protein (GFP) (AdGFP-MSCs) or IGF-I (AdIGF-I-MSCs) were applied systemically, and changes in collagen deposition and in the expression of key pro-fibrogenic and pro-regenerative genes/proteins were assessed. In addition, immunogenicity of transduced cells was analyzed. Liver fibrosis was further ameliorated after a single-dose application of AdIGF-I-MSCs when compared with AdGFP-MSCs and/or recombinant IGF-I treatments. Interestingly, an early and transitory upregulation in IGF-I and hepatocyte growth factor (HGF) mRNA expression was found in the liver of MSC-treated animals, which was more pronounced in AdIGF-I-MSCs condition. A reduction in hepatic stellate cell activation status was found after incubation with MSCs conditioned media. In addition, the AdIGF-I-MSCs cell-free supernatant induced the expression of IGF-I and HGF in primary cultured hepatocytes. From day 1 after transplantation, the proliferation marker proliferating cell nuclear antigen was upregulated in the liver of AdIGF-I-MSCs group, mainly in hepatocytes. MSCs were in vivo traced till day 14 after injection. In addition, multiple doses of Ad-IGF-I-MSCs likely suppressed antiviral immune response and it further reduced collagen deposition. Our results uncover early events that are likely involved in the anti-fibrogenic effect of genetically modified MSCs and overall would support the use of AdIGF-I-MSCs in treatment of liver fibrosis.Fil: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Bayo Fina, Juan Miguel. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Malvicini, Mariana. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Lloyd, Rodrigo. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Piccioni, Flavia Valeria. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Rizzo, Manglio Miguel. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Peixoto, Estanislao. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Sola, M. Beatriz. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Atorrasagasti, María Catalina. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Camilletti, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Enguita, Mónica. Centro de Investigación Médica Aplicada. Pamplona; EspañaFil: Prieto, Jesús. Centro de Investigación Médica Aplicada. Pamplona; EspañaFil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaMary Ann Liebert2014-12info: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/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/36546Fiore, Esteban Juan; Bayo Fina, Juan Miguel; García, Mariana Gabriela; Malvicini, Mariana; Lloyd, Rodrigo; et al.; Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice; Mary Ann Liebert; Stem Cells And Development; 24; 6; 12-2014; 791-8011547-3287CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1089/scd.2014.0174info:eu-repo/semantics/altIdentifier/url/http://online.liebertpub.com/doi/10.1089/scd.2014.0174info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:14:49Zoai:ri.conicet.gov.ar:11336/36546instacron: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 10:14:49.664CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice
title Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice
spellingShingle Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice
Fiore, Esteban Juan
Mesenchymal Stem Cells
Insulin Growth Factor-Like 1
Hgf
Liver Regeneration
Tgf-1
Hepatic Stellate Cells
Cirrhosis
title_short Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice
title_full Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice
title_fullStr Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice
title_full_unstemmed Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice
title_sort Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice
dc.creator.none.fl_str_mv Fiore, Esteban Juan
Bayo Fina, Juan Miguel
García, Mariana Gabriela
Malvicini, Mariana
Lloyd, Rodrigo
Piccioni, Flavia Valeria
Rizzo, Manglio Miguel
Peixoto, Estanislao
Sola, M. Beatriz
Atorrasagasti, María Catalina
Alaniz, Laura Daniela
Camilletti, María Andrea
Enguita, Mónica
Prieto, Jesús
Aquino, Jorge Benjamin
Mazzolini Rizzo, Guillermo Daniel
author Fiore, Esteban Juan
author_facet Fiore, Esteban Juan
Bayo Fina, Juan Miguel
García, Mariana Gabriela
Malvicini, Mariana
Lloyd, Rodrigo
Piccioni, Flavia Valeria
Rizzo, Manglio Miguel
Peixoto, Estanislao
Sola, M. Beatriz
Atorrasagasti, María Catalina
Alaniz, Laura Daniela
Camilletti, María Andrea
Enguita, Mónica
Prieto, Jesús
Aquino, Jorge Benjamin
Mazzolini Rizzo, Guillermo Daniel
author_role author
author2 Bayo Fina, Juan Miguel
García, Mariana Gabriela
Malvicini, Mariana
Lloyd, Rodrigo
Piccioni, Flavia Valeria
Rizzo, Manglio Miguel
Peixoto, Estanislao
Sola, M. Beatriz
Atorrasagasti, María Catalina
Alaniz, Laura Daniela
Camilletti, María Andrea
Enguita, Mónica
Prieto, Jesús
Aquino, Jorge Benjamin
Mazzolini Rizzo, Guillermo Daniel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mesenchymal Stem Cells
Insulin Growth Factor-Like 1
Hgf
Liver Regeneration
Tgf-1
Hepatic Stellate Cells
Cirrhosis
topic Mesenchymal Stem Cells
Insulin Growth Factor-Like 1
Hgf
Liver Regeneration
Tgf-1
Hepatic Stellate Cells
Cirrhosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Liver cirrhosis involves chronic wound healing and fibrotic processes. Mesenchymal stromal cells (MSCs) are multipotent adult progenitor cells that are used as vehicles of therapeutic genes. Insulin growth factor like-I (IGF-I) was shown to counteract liver fibrosis. We aimed at analyzing the effect of applying IGF-I overexpressing mouse bone marrow-derived MSCs on hepatic fibrosis. Fibrosis was induced by chronic thioacetamide application or bile duct ligation. MSCs engineered to produce green fluorescent protein (GFP) (AdGFP-MSCs) or IGF-I (AdIGF-I-MSCs) were applied systemically, and changes in collagen deposition and in the expression of key pro-fibrogenic and pro-regenerative genes/proteins were assessed. In addition, immunogenicity of transduced cells was analyzed. Liver fibrosis was further ameliorated after a single-dose application of AdIGF-I-MSCs when compared with AdGFP-MSCs and/or recombinant IGF-I treatments. Interestingly, an early and transitory upregulation in IGF-I and hepatocyte growth factor (HGF) mRNA expression was found in the liver of MSC-treated animals, which was more pronounced in AdIGF-I-MSCs condition. A reduction in hepatic stellate cell activation status was found after incubation with MSCs conditioned media. In addition, the AdIGF-I-MSCs cell-free supernatant induced the expression of IGF-I and HGF in primary cultured hepatocytes. From day 1 after transplantation, the proliferation marker proliferating cell nuclear antigen was upregulated in the liver of AdIGF-I-MSCs group, mainly in hepatocytes. MSCs were in vivo traced till day 14 after injection. In addition, multiple doses of Ad-IGF-I-MSCs likely suppressed antiviral immune response and it further reduced collagen deposition. Our results uncover early events that are likely involved in the anti-fibrogenic effect of genetically modified MSCs and overall would support the use of AdIGF-I-MSCs in treatment of liver fibrosis.
Fil: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Bayo Fina, Juan Miguel. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Malvicini, Mariana. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Lloyd, Rodrigo. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Piccioni, Flavia Valeria. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Rizzo, Manglio Miguel. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Peixoto, Estanislao. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Sola, M. Beatriz. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Atorrasagasti, María Catalina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Camilletti, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Enguita, Mónica. Centro de Investigación Médica Aplicada. Pamplona; España
Fil: Prieto, Jesús. Centro de Investigación Médica Aplicada. Pamplona; España
Fil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
Fil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
description Liver cirrhosis involves chronic wound healing and fibrotic processes. Mesenchymal stromal cells (MSCs) are multipotent adult progenitor cells that are used as vehicles of therapeutic genes. Insulin growth factor like-I (IGF-I) was shown to counteract liver fibrosis. We aimed at analyzing the effect of applying IGF-I overexpressing mouse bone marrow-derived MSCs on hepatic fibrosis. Fibrosis was induced by chronic thioacetamide application or bile duct ligation. MSCs engineered to produce green fluorescent protein (GFP) (AdGFP-MSCs) or IGF-I (AdIGF-I-MSCs) were applied systemically, and changes in collagen deposition and in the expression of key pro-fibrogenic and pro-regenerative genes/proteins were assessed. In addition, immunogenicity of transduced cells was analyzed. Liver fibrosis was further ameliorated after a single-dose application of AdIGF-I-MSCs when compared with AdGFP-MSCs and/or recombinant IGF-I treatments. Interestingly, an early and transitory upregulation in IGF-I and hepatocyte growth factor (HGF) mRNA expression was found in the liver of MSC-treated animals, which was more pronounced in AdIGF-I-MSCs condition. A reduction in hepatic stellate cell activation status was found after incubation with MSCs conditioned media. In addition, the AdIGF-I-MSCs cell-free supernatant induced the expression of IGF-I and HGF in primary cultured hepatocytes. From day 1 after transplantation, the proliferation marker proliferating cell nuclear antigen was upregulated in the liver of AdIGF-I-MSCs group, mainly in hepatocytes. MSCs were in vivo traced till day 14 after injection. In addition, multiple doses of Ad-IGF-I-MSCs likely suppressed antiviral immune response and it further reduced collagen deposition. Our results uncover early events that are likely involved in the anti-fibrogenic effect of genetically modified MSCs and overall would support the use of AdIGF-I-MSCs in treatment of liver fibrosis.
publishDate 2014
dc.date.none.fl_str_mv 2014-12
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/11336/36546
Fiore, Esteban Juan; Bayo Fina, Juan Miguel; García, Mariana Gabriela; Malvicini, Mariana; Lloyd, Rodrigo; et al.; Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice; Mary Ann Liebert; Stem Cells And Development; 24; 6; 12-2014; 791-801
1547-3287
CONICET Digital
CONICET
url http://hdl.handle.net/11336/36546
identifier_str_mv Fiore, Esteban Juan; Bayo Fina, Juan Miguel; García, Mariana Gabriela; Malvicini, Mariana; Lloyd, Rodrigo; et al.; Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice; Mary Ann Liebert; Stem Cells And Development; 24; 6; 12-2014; 791-801
1547-3287
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1089/scd.2014.0174
info:eu-repo/semantics/altIdentifier/url/http://online.liebertpub.com/doi/10.1089/scd.2014.0174
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
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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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