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 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

作者机构：The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Intensive Care UnitThe First Hospital of JiaxingJiaxingZhejiang ProvinceChina Department of NeurosurgeryRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2022年第17卷第12期

页      面：2717-2724页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

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

主　　题：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 

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.