White matter repair after extracellular vesicles administration in an experimental animal model of subcortical stroke
EntityInstituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)
PublisherNature Publishing Group
10.1038/srep44433Scientific Reports 7 (2017): 44433
Funded byThis study has been partially supported by grants from PS15/01318 and INVICTUS (RD12/0014) (Spanish Neurovascular Network), Miguel Servet (CP15/00069 to María Gutiérrez-Fernández) and a Sara Borrell postdoctoral fellowship (CD12/00706, to Laura Otero-Ortega) from Research Institute Carlos III, Ministry of Science and Innovation of Spain and European Regional Development Fund
ProjectGobierno de España. PS15/01318; Gobierno de España. RD12/0014
SubjectsMesenchymal stem cells; Stroke; Extracellular vesicles; Administration of EVs; Medicina
Rights© The Author(s) 2017
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50-100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers. We found that a single administration of EVs improved functional recovery, fiber tract integrity, axonal sprouting and white matter repair markers in an experimental animal model of subcortical stroke. EVs were found in the animals' brain and peripheral organs after euthanasia. White matter integrity was in part restored by EVs administration mediated by molecular repair factors implicated in axonal sprouting, tract connectivity, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery. This novel role for EVs presents a new perspective in the development of biologics for brain repair.
Google Scholar:Otero-Ortega, Laura - Laso-García, Fernando - Gómez-de Frutos, María del Carmen - Rodríguez-Frutos, Berta - Pascual-Guerra, Jorge - Fuentes Gimeno, Blanca Eulalia - Díez Tejedor, Exuperio - Gutiérrez-Fernández, María
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