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dc.contributor.authorOtero-Ortega, Laura
dc.contributor.authorGutierrez-Fernandez, Maria
dc.contributor.authorRamos-Cejudo, Jaime
dc.contributor.authorRodriguez-Frutos, Berta
dc.contributor.authorFuentes, Blanca
dc.contributor.authorSobrino, Tomas
dc.contributor.authorNavarro Hernanz, Teresa
dc.contributor.authorCampos, Francisco
dc.contributor.authorLopez, Juan Antonio 
dc.contributor.authorCerdan, Sebastian
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorDiez-Tejedor, Exuperio
dc.date.accessioned2017-11-27T13:49:51Z
dc.date.available2017-11-27T13:49:51Z
dc.date.issued2015
dc.identifierISI:000358480500001
dc.identifier.citationStem Cell Res Ther. 2015; 6(1):121
dc.identifier.issn1757-6512
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5401
dc.description.abstractIntroduction: 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 x 10(6) 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 proteom cs 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.
dc.description.sponsorshipThis 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. Avendano 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.
dc.language.isoeng
dc.publisherBioMed Central (BMC) 
dc.type.hasVersionVoR
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectBONE-MARROW
dc.subjectBRAIN
dc.subjectHEMORRHAGE
dc.subjectDELIVERY
dc.subjectMODEL
dc.subjectRAT
dc.titleWhite matter injury restoration after stem cell administration in subcortical ischemic stroke
dc.typejournal article
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID26088123
dc.format.volume6
dc.identifier.doi10.1186/s13287-015-0111-4
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1186/s13287-015-0111-4
dc.identifier.journalStem Cell Research & Therapy
dc.repisalud.orgCNICCNIC::Grupos de investigación::Proteómica cardiovascular
dc.repisalud.orgCNICCNIC::Unidades técnicas::Proteómica / Metabolómica
dc.repisalud.institucionCNIC
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución 4.0 Internacional