Therapeutic potential of extracellular vesicles derived from human mesenchymal stem cells in a model of progressive multiple sclerosis
EntityUAM. Departamento de Didáctica y Teoría de la Educación; UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)
PublisherPublic Library of Science
10.1371/journal.pone.0202590PLoS ONE 13.9 (2018): e0202590
Funded byThis study was supported by Red Española de Esclerosis Múltiple Grants RD12/ 0032/0008 and RD16/0015/0021 (sponsored by the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional [FEDER]) to C.G.
SubjectsExtracellular vesicles; Therapeutic agents; Multiple sclerosis (MS); Mesenchymal stem cells (MSCs; Intravenous EV administration; Educación; Medicina
Rights© 2018 Laso-García et al.
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and as possible therapeutic agents in inflammation-mediated demyelinating diseases, including multiple sclerosis (MS). In the present study, we investigated whether intravenously administered EVs derived from mesenchymal stem cells (MSCs) from human adipose tissue might mediate recovery in Theiler’s murine encephalomyelitis virus (TMEV)induced demyelinating disease, a progressive model of MS. SJL/J mice were subjected to EV treatment once the disease was established. We found that intravenous EV administration improved motor deficits, reduced brain atrophy, increased cell proliferation in the subventricular zone and decreased inflammatory infiltrates in the spinal cord in mice infected with TMEV. EV treatment was also capable of modulating neuroinflammation, given glial fibrillary acidic protein and Iba-1 staining were reduced in the brain, whereas myelin protein expression was increased. Changes in the morphology of microglial cells in the spinal cord suggest that EVs also modulate the activation state of microglia. The clear reduction in plasma cytokine levels, mainly in the Th1 and Th17 phenotypes, in TMEV mice treated with EVs confirms the immunomodulatory ability of intravenous EVs. According to our results, EV administration attenuates motor deficits through immunomodulatory actions, diminishing brain atrophy and promoting remyelination. Further studies are necessary to establish EV delivery as a possible therapy for the neurodegenerative phase of MS.
Google Scholar:Laso-García, Fernando - Ramos-Cejudo, Jaime - Carrillo-Salinas, Francisco Javier - Otero-Ortega, Laura - Feliú, Ana - Gómez-de Frutos, Mari Carmen - Mecha, Miriam - Díez Tejedor, Exuperio - Guaza, Carmen - Gutiérrez-Fernández, María
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Circulating extracellular vesicle proteins and microRNA profiles in subcortical and cortical-subcortical ischaemic stroke Otero-Ortega, Laura; Alonso-López, Elisa; Pérez-Mato, María; Laso-García, Fernando; Gómez-De Frutos, Mari Carmen; Diekhorst, Luke; García-Bermejo, María Laura; Conde-Moreno, Elisa; Fuentes Gimeno, Blanca Eulalia; de Leciñana, María Alonso; Bravo, Susana B.; Díez Tejedor, Exuperio; Gutiérrez-Fernández, María