摘要
Extracellular vesicles from skin-derived precursor Schwann cells(SKP-SC-EVs)promote neurite outgrowth in culture and enhance peripheral nerve regeneration in rats.This study aimed at expanding the application of SKPSC-EVs in nerve grafting by creating a chitosan/PLGA-based,SKP-SC-EVs-containing tissue engineered nerve graft(TENG)to bridge a 40-mm long sciatic nerve defect in dogs.SKP-SC-EVs contained in TENGs significantly accelerated the recovery of hind limb motor and electrophysiological functions,supported the outgrowth and myelination of regenerated axons,and alleviated the denervation-induced atrophy of target muscles in dogs.To clarify the underlying molecular mechanism,we observed that SKP-SC-EVs were rich in a variety of miRNAs linked to the axon growth of neurons,and miR-30b-5p was the most important among others.We further noted that miR-30b-5p contained within SKP-SC-EVs exerted nerve regeneration-promoting effects by targeting the Sin3a/HDAC complex and activating the phosphorylation of ERK,STAT3 or CREB.Our findings suggested that SKP-SC-EVs-incorporating TENGs represent a novel type of bioactive material with potential application for peripheral nerve repair in the clinic.
基金
supported by the Major Research Plan of the National Natural Science Foundation of China(92068112)
the National Key Research and Development Program of China(2017YFA0104700)
the National Natural Science Foundation of China(82201509)
the National Major Project of Research and Development(2022YFA1105500).
