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

Pharmaceutics

Felipe Goñi-de-Cerio¹  Marco Möller²  Irantzu Llarena²  Pedro Ramos-Cabrer²  Susana Carregal-Romero²  Imre Mäger³  LeslieA. Nash³  Matthew Wood³  M. Betanzos⁴  Leire Iparraguirre⁵  Laura Moles⁵  David Otaegui⁵  Iñaki Osorio-Querejeta⁵  Ainhoa Alberro⁵  Ander Egimendia⁵  Maider Muñoz-Culla⁵  Ana Ayerdi-Izquierdo⁶  Goran Bijelic⁶ 

[1] Biotechnology Area, Gaiker Technology Centre, 48170 Zamudio, Spain;Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo Miramón 182, 20014 Donostia , San Sebastián, Spain;Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK;Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain;Multiple Sclerosis Unit, Biodonostia Health Institute, 20014 San Sebastián, Spain;TECNALIA, Basque Research and Technology Alliance (BRTA), Mikeletegi Pasealekua 2, 20009 Donostia-San Sebastián, Spain;

关键词: multiple sclerosis;    remyelination;    myelin;    neurodegeneration;    central nervous system;    drug delivery;   

DOI  :  10.3390/pharmaceutics12020186

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown