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Chromatographic Scalable Method to Isolate Engineered Extracellular Vesicles Derived from Mesenchymal Stem Cells for the Treatment of Liver Fibrosis in Mice

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dc.contributor.author Domínguez, Luciana M.
dc.contributor.author Bueloni, Bárbara
dc.contributor.author Cantero, María José
dc.contributor.author Albornoz, Milagros
dc.contributor.author Pacienza, Natalia
dc.contributor.author Biani, María Celeste
dc.contributor.author Luzzani, Carlos Daniel
dc.contributor.author Miriuka, Santiago Gabriel
dc.contributor.author García, Mariana
dc.contributor.author Atorrasagasti Fernández, María Catalina
dc.contributor.author Yannarelli, Gustavo
dc.contributor.author Bayo, Juan
dc.contributor.author Fiore, Esteban
dc.contributor.author Mazzolini, Guillermo
dc.date.accessioned 2023-12-21T16:54:57Z
dc.date.available 2023-12-21T16:54:57Z
dc.date.issued 2023-05-31
dc.identifier.citation Domínguez LM, Bueloni B, Cantero MJ, Albornoz M, Pacienza N, Biani MC, Luzzani CD, Miriuka S, García M, Atorrasagasti C, Yannarelli G, Bayo J, Fiore E, Mazzolini G. Chromatographic Scalable Method to Isolate Engineered Extracellular Vesicles Derived from Mesenchymal Stem Cells for the Treatment of Liver Fibrosis in Mice. Int J Mol Sci. 2023 May 31;24(11):9586. doi: 10.3390/ijms24119586 es_ES
dc.identifier.uri https://doi.org/10.3390/ijms24119586
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/931
dc.description.abstract New therapeutic options for liver cirrhosis are needed. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have emerged as a promising tool for delivering therapeutic factors in regenerative medicine. Our aim is to establish a new therapeutic tool that employs EVs derived from MSCs to deliver therapeutic factors for liver fibrosis. EVs were isolated from supernatants of adipose tissue MSCs, induced-pluripotent-stem-cell-derived MSCs, and umbilical cord perivascular cells (HUCPVC-EVs) by ion exchange chromatography (IEC). To produce engineered EVs, HUCPVCs were transduced with adenoviruses that code for insulin-like growth factor 1 (AdhIGF-I-HUCPVC-EVs) or green fluorescent protein. EVs were characterized by electron microscopy, flow cytometry, ELISA, and proteomic analysis. We evaluated EVs' antifibrotic effect in thioacetamide-induced liver fibrosis in mice and on hepatic stellate cells in vitro. We found that IEC-isolated HUCPVC-EVs have an analogous phenotype and antifibrotic activity to those isolated by ultracentrifugation. EVs derived from the three MSCs sources showed a similar phenotype and antifibrotic potential. EVs derived from AdhIGF-I-HUCPVC carried IGF-1 and showed a higher therapeutic effect in vitro and in vivo. Remarkably, proteomic analysis revealed that HUCPVC-EVs carry key proteins involved in their antifibrotic process. This scalable MSC-derived EV manufacturing strategy is a promising therapeutic tool for liver fibrosis. es_ES
dc.language.iso eng es_ES
dc.publisher MDPI es_ES
dc.rights info:eu-repo/semantics/openAccess
dc.subject Extracellular Vesicles es_ES
dc.subject Vesículas Extracelulares es_ES
dc.subject Hepatic Stellate Cells es_ES
dc.subject Células Estrelladas Hepáticas es_ES
dc.subject Liver Cirrhosis es_ES
dc.subject Cirrosis Hepática es_ES
dc.subject Mesenchymal Stem Cells es_ES
dc.subject Mesenchymal Stem Cells es_ES
dc.title Chromatographic Scalable Method to Isolate Engineered Extracellular Vesicles Derived from Mesenchymal Stem Cells for the Treatment of Liver Fibrosis in Mice es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.type info:eu-repo/semantics/publishedVersion
dc.description.fil Fil: Biani, María Celeste. Fleni. Instituto de Neurociencias FLENI-CONICET. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Luzzani, Carlos Daniel. Fleni. Instituto de Neurociencias FLENI-CONICET. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Miriuka, Santiago Gabriel. Fleni. Instituto de Neurociencias FLENI-CONICET. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.relation.ispartofVOLUME 24
dc.relation.ispartofNUMBER 11
dc.relation.ispartofPAGINATION 9586
dc.relation.ispartofCOUNTRY Suiza
dc.relation.ispartofCITY Basilea
dc.relation.ispartofTITLE International journal of molecular sciences
dc.relation.ispartofISSN 1422-0067
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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