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dc.contributor.author
Fiore, Esteban Juan
dc.contributor.author
Bayo Fina, Juan Miguel
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García, Mariana Gabriela
dc.contributor.author
Malvicini, Mariana
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Lloyd, Rodrigo
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Piccioni, Flavia Valeria
dc.contributor.author
Rizzo, Manglio Miguel
dc.contributor.author
Peixoto, Estanislao
dc.contributor.author
Sola, M. Beatriz
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Atorrasagasti, María Catalina
dc.contributor.author
Alaniz, Laura Daniela
dc.contributor.author
Camilletti, María Andrea
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Enguita, Mónica
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Prieto, Jesús
dc.contributor.author
Aquino, Jorge Benjamin
dc.contributor.author
Mazzolini Rizzo, Guillermo Daniel
dc.date.available
2018-02-15T17:50:11Z
dc.date.issued
2014-12
dc.identifier.citation
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
dc.identifier.issn
1547-3287
dc.identifier.uri
http://hdl.handle.net/11336/36546
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Mary Ann Liebert
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Mesenchymal Stem Cells
dc.subject
Insulin Growth Factor-Like 1
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Hgf
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Liver Regeneration
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Tgf-1
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Hepatic Stellate Cells
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Cirrhosis
dc.subject.classification
Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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Medicina Critica y de Emergencia
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Mesenchymal stromal cells engineered to produce IGF-I by recombinant adenovirus ameliorate liver fibrosis in mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-02-14T19:28:29Z
dc.journal.volume
24
dc.journal.number
6
dc.journal.pagination
791-801
dc.journal.pais
Estados Unidos
dc.journal.ciudad
New York
dc.description.fil
Fil: Fiore, Esteban Juan. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Bayo Fina, Juan Miguel. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Malvicini, Mariana. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Lloyd, Rodrigo. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Piccioni, Flavia Valeria. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Rizzo, Manglio Miguel. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Peixoto, Estanislao. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Sola, M. Beatriz. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Atorrasagasti, María Catalina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
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
dc.description.fil
Fil: Enguita, Mónica. Centro de Investigación Médica Aplicada. Pamplona; España
dc.description.fil
Fil: Prieto, Jesús. Centro de Investigación Médica Aplicada. Pamplona; España
dc.description.fil
Fil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.description.fil
Fil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina
dc.journal.title
Stem Cells And Development
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1089/scd.2014.0174
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://online.liebertpub.com/doi/10.1089/scd.2014.0174


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