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Abstract
To identify the molecular targets of MSC-derived exosomes in treating cerebral ischemia and elucidate their therapeutic mechanisms. We utilized a mouse model of middle cerebral artery occlusion (MCAO) and treated mice with umbilical cord mesenchymal stem cells (uc-MSCs) derived exosomes. Proteomic analysis identified AAK1(AP2 associated kinase 1) as a key target protein. Functional studies confirmed that AAK1 modulates the NF-κB signaling pathway in ischemic stroke. MicroRNA profiling, bioinformatic prediction, and cell experiments identified miR-664a-5p as the specific microRNA regulating AAK1 expression. Finally, we validated the therapeutic effects of uc-MSCs-derived exosomes using engineered miR-664a-5p-deficient exosomes. Our findings demonstrate that uc-MSCs-derived exosomes exert neuroprotective effects in ischemic stroke by modulating the AAK1/NF-κB axis via miR-664a-5p. This study provides novel insights into the therapeutic mechanism of MSC-derived exosomes in ischemic stroke, highlighting their potential for developing exosome-based therapies.
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