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dc.contributor.authorHervás Salcedo, María Rosario
dc.contributor.authorFernández García, María
dc.contributor.authorHernando-Rodríguez, Miriam
dc.contributor.authorQuintana Bustamante, Óscar
dc.contributor.authorSegovia, Jose-Carlos
dc.contributor.authorAlvarez-Silva, Marcio
dc.contributor.authorGarcía Arranz, Mariano Andrés 
dc.contributor.authorMínguez, Pablo
dc.contributor.authorPozo Abejón, María Victoria del 
dc.contributor.authorRodriguez de Alba, Marta
dc.contributor.authorGarcía Olmo, Damián 
dc.contributor.authorAyuso, Carmen
dc.contributor.authorLamana, María Luisa
dc.contributor.authorBueren, Juan A.
dc.contributor.authorYañez, Rosa María
dc.contributor.otherUAM. Departamento de Cirugíaes_ES
dc.contributor.otherUAM. Departamento de Medicinaes_ES
dc.date.accessioned2022-07-22T11:30:32Z
dc.date.available2022-07-22T11:30:32Z
dc.date.issued2021-02-12
dc.identifier.citationStem Cell Research & Therapy 12.1 (2021): 124es_ES
dc.identifier.issn1757-6512es_ES
dc.identifier.urihttp://hdl.handle.net/10486/703300
dc.descriptionSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliationses_ES
dc.description.abstractBackground Mesenchymal stromal cells (MSCs) constitute one of the cell types most frequently used in cell therapy. Although several studies have shown the efficacy of these cells to modulate inflammation in different animal models, the results obtained in human clinical trials have been more modest. Here, we aimed at improving the therapeutic properties of MSCs by inducing a transient expression of two molecules that could enhance two different properties of these cells. With the purpose of improving MSC migration towards inflamed sites, we induced a transient expression of the C-X-C chemokine receptor type 4 (CXCR4). Additionally, to augment the anti-inflammatory properties of MSCs, a transient expression of the anti-inflammatory cytokine, interleukin 10 (IL10), was also induced. Methods Human adipose tissue-derived MSCs were transfected with messenger RNAs carrying the codon-optimized versions of CXCR4 and/or IL10. mRNA-transfected MSCs were then studied, first to evaluate whether the characteristic phenotype of MSCs was modified. Additionally, in vitro and also in vivo studies in an LPS-induced inflamed pad model were conducted to evaluate the impact associated to the transient expression of CXCR4 and/or IL10 in MSCs. Results Transfection of MSCs with CXCR4 and/or IL10 mRNAs induced a transient expression of these molecules without modifying the characteristic phenotype of MSCs. In vitro studies then revealed that the ectopic expression of CXCR4 significantly enhanced the migration of MSCs towards SDF-1, while an increased immunosuppression was associated with the ectopic expression of IL10. Finally, in vivo experiments showed that the co-expression of CXCR4 and IL10 increased the homing of MSCs into inflamed pads and induced an enhanced anti-inflammatory effect, compared to wild-type MSCs. Conclusions Our results demonstrate that the transient co-expression of CXCR4 and IL10 enhances the therapeutic potential of MSCs in a local inflammation mouse model, suggesting that these mRNA-modified cells may constitute a new step in the development of more efficient cell therapies for the treatment of inflammatory diseaseses_ES
dc.description.sponsorshipThis work was supported by the following public grants: Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III Ministerio de Ciencia, Innovación y Universidades and Fondo Europeo de Desarrollo Regional (FEDER) ((RETICS-RD16/0011/0011, PIE15/00048, PI18-01379), and Dirección General de Investigación de la Comunidad de Madrid (AvanCell-CM; Ref S2017/BMD-3692)es_ES
dc.format.extent20 pag.es_ES
dc.format.mimetypeapplication/pdfes_ES
dc.language.isoenges_ES
dc.publisherBiomed Central Ltd.es_ES
dc.relation.ispartofStem Cell Research and Therapyes_ES
dc.rights© The Author(s)es_ES
dc.subject.otherMesenchymal stromal cellses_ES
dc.subject.otherCXCR4es_ES
dc.subject.otherIL10es_ES
dc.subject.othermRNA-modified MSCses_ES
dc.subject.otherInflammationes_ES
dc.subject.otherMSC hominges_ES
dc.titleEnhanced anti-inflammatory effects of mesenchymal stromal cells mediated by the transient ectopic expression of CXCR4 and IL10es_ES
dc.typearticlees_ES
dc.subject.ecienciaMedicinaes_ES
dc.relation.publisherversionhttps://doi.org/10.1186/s13287-021-02193-0es_ES
dc.identifier.publicationfirstpage124-1es_ES
dc.identifier.publicationissue1es_ES
dc.identifier.publicationlastpage124-20es_ES
dc.identifier.publicationvolumeStem Cell Research and Therapyes_ES
dc.relation.projectIDComunidad de Madrid. S2017/BMD-3692es_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersiones_ES
dc.rights.ccReconocimientoes_ES
dc.rights.accessRightsopenAccesses_ES
dc.authorUAMGarcía Arranz, Mariano Andrés (262199)es_ES
dc.authorUAMPozo Abejón, María Victoria del (278827)es_ES
dc.authorUAMGarcía Olmo, Damián (259813)es_ES
dc.facultadUAMFacultad de Medicinaes_ES
dc.institutoUAMInstituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD)es_ES


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