White matter injury restoration after stem cell administration in subcortical ischemic stroke

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dc.contributor.author Otero-Ortega, Laura
dc.contributor.author Gutiérrez-Fernández, María
dc.contributor.author Ramos-Cejudo, Jaime
dc.contributor.author Rodríguez-Frutos, Berta
dc.contributor.author Fuentes, Blanca
dc.contributor.author Sobrino, Tomás
dc.contributor.author Navarro Hernanz, Teresa
dc.contributor.author Campos, Francisco
dc.contributor.author López, Juan Antonio
dc.contributor.author Cerdán, Sebastián
dc.contributor.author Vázquez, Jesús
dc.contributor.author Díez-Tejedor, Exuperio
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.contributor.other Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) es_ES
dc.contributor.other Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM) es_ES
dc.date.accessioned 2016-08-04T13:47:24Z
dc.date.available 2016-08-04T13:47:24Z
dc.date.issued 2015-06-19
dc.identifier.citation Stem Cell Research and Therapy 6.1 (2015): 121 en_US
dc.identifier.issn 1757-6512 es_ES
dc.identifier.uri http://hdl.handle.net/10486/672376
dc.description.abstract Introduction: Despite its high incidence, nerve fiber (axon and myelin) damage after cerebral infarct has not yet been extensively investigated. The aim of this study was to investigate white matter repair after adipose-derived mesenchymal stem cell (ADMSC) administration in an experimental model of subcortical stroke. Furthermore, we aimed to analyze the ADMSC secretome and whether this could be implicated in this repair function. Methods: An animal model of subcortical ischemic stroke with white matter affectation was induced in rats by injection of endothelin-1. At 24 hours, 2 × 106 ADMSC were administered intravenously to the treatment group. Functional evaluation, lesion size, fiber tract integrity, cell death, proliferation, white matter repair markers (Olig-2, NF, and MBP) and NogoA were all studied after sacrifice (7 days and 28 days). ADMSC migration and implantation in the brain as well as proteomics analysis and functions of the secretome were also analyzed. Results: Neither ADMSC migration nor implantation to the brain was observed after ADMSC administration. In contrast, ADMSC implantation was detected in peripheral organs. The treatment group showed a smaller functional deficit, smaller lesion area, less cell death, more oligodendrocyte proliferation, more white matter connectivity and higher amounts of myelin formation. The treated animals also showed higher levels of white matter-associated markers in the injured area than the control group. Proteomics analysis of the ADMSC secretome identified 2,416 proteins, not all of them previously described to be involved in brain plasticity. Conclusions: White matter integrity in subcortical stroke is in part restored by ADMSC treatment; this is mediated by repair molecular factors implicated in axonal sprouting, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery after stroke en_US
dc.description.sponsorship This study was supported by research grants PS12/01754, PI11/00909 and INVICTUS (RD12/0014) (Spanish Neurovascular Network), SAF2010-37926, ProteoRed-PT13/0001/0017 and a Sara Borrell postdoctoral fellowship (CD12/00706, to LOO) from Research Institute Carlos III, Ministry of Science and Innovation of Spain. We greatly appreciate advice from Prof. Avendaño and Dr Negredo and we thank ServingMed.com for linguistic assistance. Furthermore, TS (CP12/03121) and FC (CP14/00154) are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos III en_US
dc.format.extent 12 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher BioMed Central en_US
dc.relation.ispartof Stem Cell Research and Therapy en_US
dc.rights © 2015 Otero-Ortega et al. es_ES
dc.subject.other White matter en_US
dc.subject.other Mesenchymal stem cell en_US
dc.subject.other Axonal sprouting en_US
dc.title White matter injury restoration after stem cell administration in subcortical ischemic stroke en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion http://dx.doi.org/10.1186/s13287-015-0111-4 es_ES
dc.identifier.doi 10.1186/s13287-015-0111-4 es_ES
dc.identifier.publicationfirstpage 121-1 es_ES
dc.identifier.publicationissue 1 es_ES
dc.identifier.publicationlastpage 121-12 es_ES
dc.identifier.publicationvolume 6 es_ES
dc.relation.projectID Gobierno de España. SAF2010-37926 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Díez Tejedor, Exuperio (258291)
dc.authorUAM Fuentes Gimeno, Blanca Eulalia (262687)

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