Central
nervous system (CNS) injuries, including stroke, traumatic brain
injury, and spinal cord injury, are essential causes of death and
long-term disability and difficult to cure, mainly due to the limited
neuron regeneration and the formation of the glial scar. Herein, we
apply extracellular vesicles (EVs) secreted by M2 microglia to improve
the differentiation of neural stem cells (NSCs) at the injured site, and
simultaneously modify them with the injured vascular targeting peptide
(DA7R) and the stem cell recruiting factor (SDF-1) on their surface via
copper-free click chemistry to recruit NSCs, inducing their neuronal
differentiation, and serving as the nanomissiles at the injured site
(Dual-EV). Results prove that the Dual-EV holds the ability to target
human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and
promote the neuronal differentiation of NSCs in vitro. 10 miRNAs were found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via
bioinformatic analysis, and further NSC differentiation experiment by
flow cytometry revealed that among these miRNAs, miR30b-3p, miR-222-3p,
miR-129-5p, and miR-155-5p may exert effect of inducing NSC to
differentiate into neurons. In vivo experiments show that
Dual-EV nanomissiles achieve improved accumulation in the ischemic area
of stroke model mice, potentiate NSCs recruitment, and increase
neurogenesis. This work provides new insights for the treatment of
neuronal regeneration after CNS injuries as well as endogenous stem
cells, and the click chemistry EV/peptide/chemokine and related
nanomissiles for improving human health.
No comments:
Post a Comment