White matter injury restoration after stem cell administration in subcortical ischemic stroke
EntityUAM. Departamento de Medicina; Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ); Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
10.1186/s13287-015-0111-4Stem Cell Research and Therapy 6.1 (2015): 121
Funded byThis 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
ProjectGobierno de España. SAF2010-37926
SubjectsWhite matter; Mesenchymal stem cell; Axonal sprouting; Medicina
Rights© 2015 Otero-Ortega et al.
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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
Google Scholar:Otero-Ortega, Laura - Gutiérrez-Fernández, María - Ramos-Cejudo, Jaime - Rodríguez-Frutos, Berta - Fuentes Gimeno, Blanca Eulalia - Sobrino, Tomás - Navarro Hernanz, Teresa - Campos, Francisco - López, Juan Antonio - Cerdán, Sebastián - Vázquez, Jesús - Díez Tejedor, Exuperio
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