Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Otero-Ortega, Laura, Laso-García, Fernando, Frutos, Mari Carmen Gómez-de, Diekhorst, Luke, Martínez-Arroyo, Arturo, Alonso-López, Elisa, García-Bermejo, María Laura, Rodríguez-Serrano, Macarena, Arrúe-Gonzalo, Mercedes, Díez-Tejedor, Exuperio, Fuentes, Blanca, Gutiérrez-Fernández, María
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029550/
https://www.ncbi.nlm.nih.gov/pubmed/32075692
http://dx.doi.org/10.1186/s13287-020-01601-1
_version_ 1783499192493146112
author Otero-Ortega, Laura
Laso-García, Fernando
Frutos, Mari Carmen Gómez-de
Diekhorst, Luke
Martínez-Arroyo, Arturo
Alonso-López, Elisa
García-Bermejo, María Laura
Rodríguez-Serrano, Macarena
Arrúe-Gonzalo, Mercedes
Díez-Tejedor, Exuperio
Fuentes, Blanca
Gutiérrez-Fernández, María
author_facet Otero-Ortega, Laura
Laso-García, Fernando
Frutos, Mari Carmen Gómez-de
Diekhorst, Luke
Martínez-Arroyo, Arturo
Alonso-López, Elisa
García-Bermejo, María Laura
Rodríguez-Serrano, Macarena
Arrúe-Gonzalo, Mercedes
Díez-Tejedor, Exuperio
Fuentes, Blanca
Gutiérrez-Fernández, María
author_sort Otero-Ortega, Laura
collection PubMed
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.
format Online
Article
Text
id pubmed-7029550
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-70295502020-02-25 Low dose of extracellular vesicles identified that promote recovery after ischemic stroke Otero-Ortega, Laura Laso-García, Fernando Frutos, Mari Carmen Gómez-de Diekhorst, Luke Martínez-Arroyo, Arturo Alonso-López, Elisa García-Bermejo, María Laura Rodríguez-Serrano, Macarena Arrúe-Gonzalo, Mercedes Díez-Tejedor, Exuperio Fuentes, Blanca Gutiérrez-Fernández, María Stem Cell Res Ther Research 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. BioMed Central 2020-02-19 /pmc/articles/PMC7029550/ /pubmed/32075692 http://dx.doi.org/10.1186/s13287-020-01601-1 Text en © The Author(s) 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Otero-Ortega, Laura
Laso-García, Fernando
Frutos, Mari Carmen Gómez-de
Diekhorst, Luke
Martínez-Arroyo, Arturo
Alonso-López, Elisa
García-Bermejo, María Laura
Rodríguez-Serrano, Macarena
Arrúe-Gonzalo, Mercedes
Díez-Tejedor, Exuperio
Fuentes, Blanca
Gutiérrez-Fernández, María
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
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_short 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029550/
https://www.ncbi.nlm.nih.gov/pubmed/32075692
http://dx.doi.org/10.1186/s13287-020-01601-1
work_keys_str_mv AT oteroortegalaura lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT lasogarciafernando lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT frutosmaricarmengomezde lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT diekhorstluke lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT martinezarroyoarturo lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT alonsolopezelisa lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT garciabermejomarialaura lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT rodriguezserranomacarena lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT arruegonzalomercedes lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT dieztejedorexuperio lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT fuentesblanca lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke
AT gutierrezfernandezmaria lowdoseofextracellularvesiclesidentifiedthatpromoterecoveryafterischemicstroke