Although adipose derived stem cells (ADSCs) exert their therapeutic potential in ischemic stroke, the migration of ADSCs in injured area is not apparently observed after intravenous administration. ADSCs are an important source of exosomes which hold great promise as an endogenous drug delivery system for the treatment of cerebral ischemia given their ability to cross the blood-brain barrier. Here we investigated whether ADSCs-derived exosomes mediated miRNAs transfer and thus promoted neurological recovery after stroke. We first proved that miR-126 levels were reduced in patients' plasma with acute ischemic stroke and in rat plasma and brain tissue after ischemia. To test the effect of exosomal miR-126, we employed overexpression and knock-down technologies to up-regulate or inhibit miR-126 level in ADSCs and thus acquired miR-126 exosomes and miR-126 exosomes, respectively. Compared with control, systemic administration of ADSCs-derived exosomes significantly increased the expression of von Willebrand factor (an endothelia cell marker) and doublecortin (a neuroblasts marker) and improved functional recovery in stroke rats. ADSCs-derived exosomes also resulted in a decrease of neuron cell death and an increase of cell proliferation compared with control. Importantly, these outcomes were further enhanced with miR-126 exosomes treatment and were significantly decreased with miR-126 exosomes treatment, compared to naïve exosomes treatment. MiR-126 exosomes also inhibited microglial activation and the expression of inflammatory factors and . Our results suggest that intravenous administration of miR-126 exosomes post stroke improves functional recovery, enhances neurogenesis, inhibits neuroinflammation, and represents a novel treatment for stroke.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413259PMC

Publication Analysis

Top Keywords

mir-126 exosomes
24
exosomes
12
functional recovery
12
recovery stroke
12
adscs-derived exosomes
12
exosomes treatment
12
mir-126
9
stroke rats
8
ischemic stroke
8
intravenous administration
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!