MiR-219a-5p Enriched Extracellular Vesicles Induce OPC Differentiation and EAE Improvement More Efficiently Than Liposomes and Polymeric Nanoparticles
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2020-02
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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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Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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Multiple sclerosis , Remyelination , Myelin , Neurodegeneration , Central nervous system , Drug delivery , Multiple sclerosis , Remyelination , Myelin , Neurodegeneration , Central nervous system , Drug delivery , Pharmaceutical Science , SDG 3 - Good Health and Well-being , Funding Info , This work was supported by Carlos III Institute, (PI17/00189 and DTS15/00069), by Fondo Europeo_x000D_ de Desarrollo Regional—FEDER, by the Gipuzkoa Regional Council (DFG 15/006), by grant from the Basque_x000D_ Government (RIS3/DTS/2018222025), by the Department of Industry of the Basque Country (ELKARTEK 16/014),_x000D_ and the Spanish State Research Agency (SAF2017-87670-R) and Maria de Maeztu Units of Excellence Program_x000D_ Grant MDM-2017-0720). I.O.-Q., A.A. and L.I. were supported by the Department of Education of the Basque_x000D_ Government. IOQ and LAN were supported by EMBO short Term Fellowship Programme. LAN was supported_x000D_ by a Canadian graduate scholarship from the Canadian Institutes of Health Research (CGS-D CIHR).PRC was_x000D_ supported by Ikerbasque, the Basque Foundation for Science. , This work was supported by Carlos III Institute, (PI17/00189 and DTS15/00069), by Fondo Europeo_x000D_ de Desarrollo Regional—FEDER, by the Gipuzkoa Regional Council (DFG 15/006), by grant from the Basque_x000D_ Government (RIS3/DTS/2018222025), by the Department of Industry of the Basque Country (ELKARTEK 16/014),_x000D_ and the Spanish State Research Agency (SAF2017-87670-R) and Maria de Maeztu Units of Excellence Program_x000D_ Grant MDM-2017-0720). I.O.-Q., A.A. and L.I. were supported by the Department of Education of the Basque_x000D_ Government. IOQ and LAN were supported by EMBO short Term Fellowship Programme. LAN was supported_x000D_ by a Canadian graduate scholarship from the Canadian Institutes of Health Research (CGS-D CIHR).PRC was_x000D_ supported by Ikerbasque, the Basque Foundation for Science.
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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 2020 , ' MiR-219a-5p Enriched Extracellular Vesicles Induce OPC Differentiation and EAE Improvement More Efficiently Than Liposomes and Polymeric Nanoparticles ' , Pharmaceutics , vol. 12 , no. 2 , 186 , pp. 186 . https://doi.org/10.3390/pharmaceutics12020186