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

• Published in: Neural regeneration research Vol. 17; no. 12; pp. 2717 - 2724
• Main Authors: Wen, Liang, Wang, Ya-Dong, Shen, Dong-Feng, Zheng, Pei-Dong, Tu, Meng-Di, You, Wen-Dong, Zhu, Yuan-Run, Wang, Hao, Feng, Jun-Feng, Yang, Xiao-Feng
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.12.2022; Medknow Publications & Media Pvt. Ltd; The First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,Zhejiang Province,China%Department of Intensive Care Unit,The First Hospital of Jiaxing,Jiaxing,Zhejiang Province,China%Department of Neurosurgery,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,China; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: Apoptosis; 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; Bone marrow; Cytokines; Genotype & phenotype; MicroRNAs; Stem cells; Traumatic brain injury; phenotype; BV2 microglia; neuroinflammation; traumatic brain injury; apoptosis; signal transducer and activator of transcription 3; lentiviral transfection; bone marrow mesenchymal stem cells; exosome; interleukin 10; microRNA-181b
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.339489

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.