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MiR-219a-5p Enriched Extracellular Vesicles Induce OPC Differentiation and EAE Improvement More Efficiently Than Liposomes and Polymeric Nanoparticles

Osorio-Querejeta, Iñaki, Carregal-Romero, Susana, Ayerdi-Izquierdo, Ana, Mäger, Imre, Nash, Leslie A., Wood, Matthew, Egimendia, Ander, Betanzos, M., Alberro, Ainhoa, Iparraguirre, Leire, Moles, Laura, Llarena, Irantzu, Möller, Marco, Goñi-de-Cerio, Felipe, Bijelic, Goran, Ramos-Cabrer, Pedro, Muñoz-Culla, Maider, Otaegui, David·2020·Pharmaceutics
DOI 10.3390/pharmaceutics12020186PMC PMC7076664
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Abstract

Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood–brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use of extracellular vesicles as miR-219a-5p delivery system can be a feasible and promising strategy to induce remyelination in multiple sclerosis patients.

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Metadata

Authors
Osorio-Querejeta, I., Carregal-Romero, S., Ayerdi-Izquierdo, A., Mäger, I., Nash, L. A., Wood, M., Egimendia, A., Betanzos, M., Alberro, A., Iparraguirre, L., Moles, L., Llarena, I., Möller, M., Goñi-de-Cerio, F., Bijelic, G., Ramos-Cabrer, P., Muñoz-Culla, M., & Otaegui, D.
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2020-02-21
Volume
12
Issue
2
Pages
186
ISSN
1999-4923
DOI
10.3390/pharmaceutics12020186
PMC
PMC7076664
Cited by
85
References
4
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • Instituto de Salud Carlos III (PI17/00189 and DTS15/00069)
  • Gipuzkoa Regional Council (DFG 15/006)
  • European Regional Development Fund (PI17/00189 and DTS15/00069)
  • Eusko Jaurlaritza (RIS3/DTS/2018222025)
  • Spanish Estate Reserach Agency (SAF2017-87670-R)

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