miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells  

作　　者：Meng Cong Jing-Jing Hu Yan Yu Xiao-Li Li Xiao-Ting Sun Li-Ting Wang Xia Wu Ling-Jie Zhu Xiao-Jia Yang Qian-Ru He Fei Ding Hai-Yan Shi 

机构地区：[1]School of Medicine,Nantong University,Nantong,Jiangsu Province,China [2]Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education and Coinnovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu Province,China [3]Department of Physiology,Jiangsu Health Vocational College,Nanjing,Jiangsu Province,China [4]Department of Pathology,Affiliated Hospital of Nantong University,Nantong,Jiangsu Province,China [5]Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair,Affiliated Hospital of Nantong University,Nantong,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2025年第1期277-290,共14页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.31870977(to HYS);the National Key Technologies Research and Development Program of China,No.2017YFA0104700(to FD);2022 Jiangsu Funding Program for Excellent Postdoctoral Talent(to MC);Priority Academic Program Development of Jiangsu Higher Education Institutions[PAPD];the Major Project of Basic Science(Natural Science)Research in Higher Education Institutions of Jiangsu Province,No.22KJA180001(to QRH)。

摘　　要：Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in

关 键 词：AXOTOMY cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors 

分 类 号：R741[医药卫生—神经病学与精神病学]