Low dose of extracellular vesicles identified that promote recovery after ischemic stroke
Background: Mesenchymal stem cell-derived extracellular vesicles (EVs) are one of the most promising therapeutics in protective and/or regenerative therapy in animal models of stroke using a dose of 100 μg. However, whether EVs dose is related to outcomes is not known. This study aimed to identify t...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/713444 |
| Acceso en línea: | http://hdl.handle.net/10486/713444 https://dx.doi.org/10.1186/s13287-020-01601-1 |
| Access Level: | acceso abierto |
| Palabra clave: | brain repair extracellular vesicles oxygen and glucose deprivation subcortical stroke white matter lesion Medicina |
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Low dose of extracellular vesicles identified that promote recovery after ischemic strokeOtero Ortega, LauraLaso García, FernandoGómez de Frutos, Mari CarmenDiekhorst, LukeMartínez Arroyo, ArturoAlonso López, ElisaGarcía Bermejo, María LauraRodríguez Serrano, MacarenaArrúe Gonzalo, MercedesDíez Tejedor, ExuperioFuentes Gimeno, Blanca EulaliaGutiérrez Fernández, Maríabrain repairextracellular vesiclesoxygen and glucose deprivationsubcortical strokewhite matter lesionMedicinaBackground: Mesenchymal stem cell-derived extracellular vesicles (EVs) are one of the most promising therapeutics in protective and/or regenerative therapy in animal models of stroke using a dose of 100 μg. However, whether EVs dose is related to outcomes is not known. This study aimed to identify the optimal effective dose of EVs from adipose tissue-derived mesenchymal stem cells that promote functional recovery in subcortical stroke. Materials and methods: For this purpose, various doses of EVs were tested in an in vitro oxygen-glucose deprivation (OGD) model of oligodendrocytes and neuronal ischemia. At least 50 μg of EVs were necessary to induce proliferation and differentiation of oligodendrocyte and neurons in OGD conditions. For in vivo study, rats were subjected to subcortical stroke and various doses (50 μg, 100 μg, or 200 μg) of EVs were intravenously administered after 24 h. Results: All the animals in the EV groups showed significant improvement in functional tests, with an increase in tract connectivity and brain repair-associated markers, and a decrease in cell death and in astrocyte-marker expression. Cell proliferation was increased in the groups receiving 50 μg and 100 μg doses. Only the 50-μg dose was associated with significant increases in brain-derived neurotrophic factor expression. Conclusion: In conclusion, 50 μg of EVs appears to be the minimal effective dose to enhance protection, brain repair, and recovery in subcortical ischemic strokeFunded by a grant (FIS PS15/01318) from the Spanish Ministry of Health—Carlos III Health Institute (ISCIII) and the European Regional Development Fund (FEDER Funding); Miguel Servet (CP15/00069 to María Gutiérrez-Fernández) and predoctoral fellowship (FI17/00188 to Mari Carmen Gómez-de Frutos, FI18/00026 to Fernando Laso-García) and the INVICTUS PLUS Spanish Network (RD16/0019/0005) of the Carlos III Health Institute (ISCIII), and Juan de la Cierva postdoctoral fellowship (IJCI-2017-33505, to Laura Otero-Ortega, Spanish State Research Agency), Spanish Ministry of Science and Innovation. We greatly appreciate the support of Morote for the editing assistanceBMCDepartamento de MedicinaFacultad de Medicina20202020-02-19research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/713444https://dx.doi.org/10.1186/s13287-020-01601-1reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7134442026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
Low dose of extracellular vesicles identified that promote recovery after ischemic stroke |
| title |
Low dose of extracellular vesicles identified that promote recovery after ischemic stroke |
| spellingShingle |
Low dose of extracellular vesicles identified that promote recovery after ischemic stroke Otero Ortega, Laura brain repair extracellular vesicles oxygen and glucose deprivation subcortical stroke white matter lesion Medicina |
| title_short |
Low dose of extracellular vesicles identified that promote recovery after ischemic stroke |
| title_full |
Low dose of extracellular vesicles identified that promote recovery after ischemic stroke |
| title_fullStr |
Low dose of extracellular vesicles identified that promote recovery after ischemic stroke |
| title_full_unstemmed |
Low dose of extracellular vesicles identified that promote recovery after ischemic stroke |
| title_sort |
Low dose of extracellular vesicles identified that promote recovery after ischemic stroke |
| dc.creator.none.fl_str_mv |
Otero Ortega, Laura Laso García, Fernando Gómez de Frutos, Mari Carmen Diekhorst, Luke Martínez Arroyo, Arturo Alonso López, Elisa García Bermejo, María Laura Rodríguez Serrano, Macarena Arrúe Gonzalo, Mercedes Díez Tejedor, Exuperio Fuentes Gimeno, Blanca Eulalia Gutiérrez Fernández, María |
| author |
Otero Ortega, Laura |
| author_facet |
Otero Ortega, Laura Laso García, Fernando Gómez de Frutos, Mari Carmen Diekhorst, Luke Martínez Arroyo, Arturo Alonso López, Elisa García Bermejo, María Laura Rodríguez Serrano, Macarena Arrúe Gonzalo, Mercedes Díez Tejedor, Exuperio Fuentes Gimeno, Blanca Eulalia Gutiérrez Fernández, María |
| author_role |
author |
| author2 |
Laso García, Fernando Gómez de Frutos, Mari Carmen Diekhorst, Luke Martínez Arroyo, Arturo Alonso López, Elisa García Bermejo, María Laura Rodríguez Serrano, Macarena Arrúe Gonzalo, Mercedes Díez Tejedor, Exuperio Fuentes Gimeno, Blanca Eulalia Gutiérrez Fernández, María |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Medicina Facultad de Medicina |
| dc.subject.none.fl_str_mv |
brain repair extracellular vesicles oxygen and glucose deprivation subcortical stroke white matter lesion Medicina |
| topic |
brain repair extracellular vesicles oxygen and glucose deprivation subcortical stroke white matter lesion Medicina |
| description |
Background: Mesenchymal stem cell-derived extracellular vesicles (EVs) are one of the most promising therapeutics in protective and/or regenerative therapy in animal models of stroke using a dose of 100 μg. However, whether EVs dose is related to outcomes is not known. This study aimed to identify the optimal effective dose of EVs from adipose tissue-derived mesenchymal stem cells that promote functional recovery in subcortical stroke. Materials and methods: For this purpose, various doses of EVs were tested in an in vitro oxygen-glucose deprivation (OGD) model of oligodendrocytes and neuronal ischemia. At least 50 μg of EVs were necessary to induce proliferation and differentiation of oligodendrocyte and neurons in OGD conditions. For in vivo study, rats were subjected to subcortical stroke and various doses (50 μg, 100 μg, or 200 μg) of EVs were intravenously administered after 24 h. Results: All the animals in the EV groups showed significant improvement in functional tests, with an increase in tract connectivity and brain repair-associated markers, and a decrease in cell death and in astrocyte-marker expression. Cell proliferation was increased in the groups receiving 50 μg and 100 μg doses. Only the 50-μg dose was associated with significant increases in brain-derived neurotrophic factor expression. Conclusion: In conclusion, 50 μg of EVs appears to be the minimal effective dose to enhance protection, brain repair, and recovery in subcortical ischemic stroke |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-02-19 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/713444 https://dx.doi.org/10.1186/s13287-020-01601-1 |
| url |
http://hdl.handle.net/10486/713444 https://dx.doi.org/10.1186/s13287-020-01601-1 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
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BMC |
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BMC |
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reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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