Title : Neural stem cell-derived exosomal mir-9a-5p overexpression improving neurogenesis in ischemic stroke
Abstract:
Background: Ischemic stroke is a serious disease which can result in physical disability and death. The protective effect of miRNA up-regulated exosomes derived from neural stem cells (NSCs) on ischemic stroke and its molecular mechanism were investigated, aiming to reveal the therapeutic target of exosome and provide new ideas for ischemic stroke.
Methods: The miRNAs differentially expressed in exosomes derived from NSC at different differentiation periods were detected by miRNA high-throughput sequencing technology. The effects of up-regulating miR-9a-5p were assessed on proliferation and differentiation of NSCs. The different effects between exosomes derived from normal and miR-9a-5p up-regulated NSCs on cell survival, proliferation, differentiation and AMPK activation were investigated in vitro and in vivo.
Results: RNA high-throughput sequencing analysis showed that miR-9a-5p was differentially expressed of NSC-derived exosomes of at different stages. Up-regulation of miR-9a-5p exosomes promote cell proliferation and differentiation of NSCs after OGD/R, and the apoptosis was reduced significantly. The vivo study revealed that miR-9a-5p exosomes decrease the infarct volume and BBB permeability of ischemic stroke. The apoptosis of neuron, astrocytes and oligodendrocytes were improved, which suggested that miR-9a-5p have the ability to regulate the differentiation of endogenic NSCs. AMPK activation was increased in MACO/R rat with miR-9a-5p exosomes.
Conclusion: miR-9a-5p exosomes promote AMPK phosphorylation and HIF-1α, so as to promote NSC survival, proliferation, migration and differentiation, which have ability to protect ischemic stroke. MiR-9a-5p is a potential therapeutic target for ischemic stroke. Exosomes are a potential drug carrier, and it is feasible to artificially modify the components of exosomes.
