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Osorio-Querejeta, Iñaki; Ayerdi, Ana; Carregal-Romero, Susana; Nash, Leslie; Alberro, Ainhoa; Iparraguirre, Leire; Mäger, Imer; Wood, Matthew J A; Ramos-Cabrer, Pedro; Muñoz-Culla, Maider; Otaegui, David
Journal of extracellular vesicles, 01/2018, Letnik: 7Journal Article
Background: Multiple sclerosis is an autoimmune and demyelinating disease of the central nervous system. Commercially available treatments are focused in the attenuation of the immune response, but up to now, none of them are focused in improving remyelination. Nevertheless, alternative strategies are being studied. MicroRNAs have been shown to work as remyelination inductors. More concretely, miR-219 has been shown to be involved in the differentiation of oligodendrocyte precursor cells (OPCs) and therefore remyelination. In this work, nanoparticles (NPs), liposomes (LPs) and exosomes (EXs) were compared as miR-219 delivery systems in an OPC culture where the ability of miR-219 to induce OPC differentiation was also analysed. Methods: OPCs were obtained from P-1 mice brains and cultured in laminin-coated P24 plates prior to the treatment. PLGA nanoparticles and DSPC liposomes were loaded with miRIDIAN microRNA mmu-miR-219a-5p. Exosomes were obtained from HEK293T cells infected with pLKO-mmu-miR219a-5p plasmid. All the respective controls were done. For uptake experiments, NPs were loaded with coumarin and LP with DiOC18. In addition, miRIDIAN microRNA mimic transfection control with Dy547 was used for NP and LP. Exosomes were labelled with Celltracker CM-Dil. In order to quantify the differentiation degree of OPCs and the levels of miR-219 in the vehicles, qPCR was carried out. Results: Preliminary results showed higher levels of miR-219 and a better uptake for LPs and NPs in comparison with EXs. However, LPs and NPs were not able to induce OPCs differentiation whereas EXs did. Summary/conclusion: EX, which showed the lowest miR-219 and uptake levels, were able to induce OPCs differentiation. These results might indicate that EX are extremely efficient as microRNA delivery systems. In addition, we hypothesized that the additional cargo that EXs may carry could favour the shown effects.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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