Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury  

作　　者：Liang Wen Ya-Dong Wang Dong-Feng Shen Pei-Dong Zheng Meng-Di Tu Wen-Dong You Yuan-Run Zhu Hao Wang Jun-Feng Feng Xiao-Feng Yang 

机构地区：[1]The First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,Zhejiang Province,China [2]Department of Intensive Care Unit,The First Hospital of Jiaxing,Jiaxing,Zhejiang Province,China [3]Department of Neurosurgery,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,China

出　　处：《Neural Regeneration Research》2022年第12期2717-2724,共8页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China, Nos.81971159(to LW), 81771317(to JFF)

摘　　要：Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair.However,the underlying molecular mechanism remains unclear.In this study,we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation.Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype,inhibited the expression of proinflammatory cytokines,and increased the expression of anti-inflammatory cytokines.Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury,inhibited neuroinflammation,and promoted the transformation of microglia to the anti-inflammatory phenotype.We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process.Finally,we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection.We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype.The interleukin 10/STAT3 pathway was activated during this process.These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.

关 键 词：apoptosis bone marrow mesenchymal stem cells BV2 microglia EXOSOME interleukin 10 lentiviral transfection microRNA-181b NEUROINFLAMMATION phenotype signal transducer and activator of transcription 3 traumatic brain injury 

分 类 号：R651.15[医药卫生—外科学]