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

1
Multiple Sclerosis Unit, Biodonostia Health Institute, 20014 San Sebastián, Spain
2
Spanish Network of Multiple Sclerosis, 08028 Barcelona, Spain
3
Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo Miramón 182, 20014 Donostia , San Sebastián, Spain
4
CIBER de Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain
5
TECNALIA, Basque Research and Technology Alliance (BRTA), Mikeletegi Pasealekua 2, 20009 Donostia-San Sebastián, Spain
6
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK
7
Department of Biochemistry, Microbiology and Immunology (BMI), University of Ottawa, 75 Laurier Ave E, Ottawa, ON K1N 6N5, Canada
8
Biotechnology Area, Gaiker Technology Centre, 48170 Zamudio, Spain
9
Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(2), 186; https://doi.org/10.3390/pharmaceutics12020186
Received: 27 November 2019 / Revised: 14 February 2020 / Accepted: 18 February 2020 / Published: 21 February 2020
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. View Full-Text
Keywords: multiple sclerosis; remyelination; myelin; neurodegeneration; central nervous system; drug delivery multiple sclerosis; remyelination; myelin; neurodegeneration; central nervous system; drug delivery
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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. MiR-219a-5p Enriched Extracellular Vesicles Induce OPC Differentiation and EAE Improvement More Efficiently Than Liposomes and Polymeric Nanoparticles. Pharmaceutics 2020, 12, 186.

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