1995中国现代医学杂志China Journal of Modern MedicineChina Journal of Modern Medicine中国现代医学杂志1005-898243-1225/R湖南省长沙市1005-8982(2022)14-0061-0510.3969/j.issn.1005-8982.2022.14.011M20210195综述R394.2AReview间充质干细胞源性外泌体抑制创伤性脑损伤炎症反应的研究进展Research progress of the roles of mesenchymal stem cells-derived exosomes in inhibiting the inflammatory response in traumatic brain injury王文瑞WangWen-rui黄晓飞HuangXiao-fei孙田静SunTian-jing刘思佳LiuSi-jia胡权HuQuan高甜GaoTian喻安永YuAn-yong遵义医科大学附属医院 急诊科, 贵州遵义563000Department of Emergency Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou563000, China李科喻安永,E-mail:anyongyu750811@126.com30072022321439616561-6509082021
There are about 800,000 patients suffering from traumatic brain injury (TBI) in China each year. The mortality of patients with severe TBI is about 27%. TBI is the leading cause of death and disability among young adults and has a great impact on society and families. According to the pathophysiology, TBI is divided into primary brain injury and secondary brain injury. Primary brain injury is a direct result of mechanical factors, while secondary brain injury is based on the original brain injury. Both the extracranial injury and intracranial physical and biochemical changes are tightly associated with the prognosis of TBI, among which a series of cascade reactions at the levels of molecules, cells, tissues and organs caused by neuroinflammatory responses play a particularly important role in the development of secondary brain injury. The mesenchymal stem cells-derived exosomes (MSC-Exo) are a promising strategy for treating brain injury. They can effectively reduce the neuroinflammatory response and improve the prognosis of TBI. This review summarizes the mechanisms of MSC-Exo inhibiting the neuroinflammatory response after TBI and their therapeutic potentials, in order to provide a reference for future research and treatment.
WANG W R, HUANG X F, SUN T J, et al. Research progress of the roles of mesenchymal stem cells-derived exosomes in inhibiting the inflammatory response in traumatic brain injury*[J]. China Journal of Modern Medicine, 2022, 32(14): 61-65.
参 考 文 献JIANG J Y, GAO G Y, FENG J F, et al. Traumatic brain injury in China[J]. Lancet Neurol, 2019, 18(3): 286-295.JAMJOOM A A B, RHODES J, ANDREWS P J D, et al. The synapse in traumatic brain injury[J]. Brain, 2021, 144(1): 18-31.LIN C T, LECCA D, YANG L Y, et al. 3,6'-dithiopomalidomide reduces neural loss, inflammation, behavioral deficits in brain injury and microglial activation[J]. Elife, 2020, 9(7): 114-128.XU H Y, JIA Z L, MA K, et al. Protective effect of BMSCs-derived exosomes mediated by BDNF on TBI via miR-216a-5p[J]. Med Sci Monit, 2020, 9(26): e920855.李佳蕊, 罗本燕. 神经炎症反应在动物创伤性脑损伤中的研究进展[J]. 国际神经病学神经外科学杂志, 2019, 46(2): 214-217.DEVANNEY N, STEWART A, GENSEL J. Microglia and macrophage metabolism in CNS injury and disease: the role of immunometabolism in neurodegeneration and neurotrauma[J]. Exp Neurol, 2020, 7(329): 113310.ZHANG Z, LIANG J, YAN J X, et al. TBHQ improved neurological recovery after traumatic brain injury by inhibiting the overactivation of astrocytes[J]. Brain Res, 2020, 17(39): 146818.TANG B, SONG M, XIE X, et al. Tumor necrosis factor-stimulated gene-6 (TSG-6) secreted by BMSCs regulates activated astrocytes by inhibiting NF-κB signaling pathway to ameliorate blood brain barrier damage after intracerebral hemorrhage[J]. Neurochem Res, 2021, 14(6): 273-281.DINET V, PETRY K G, BADAUT J. Brain-immune interactions and neuroinflammation after traumatic brain injury[J]. Front Neurosci, 2019, 13(1): 178-184.张震文, 严菁兴, 彭晓明, 等. 人脐带间充质干细胞外泌体对创伤性脑损伤后神经功能的保护作用[J]. 中华行为医学与脑科学杂志, 2020, 29(12): 1061-1066.CHEN Y F, LI J, MA B T, et al. MSC-derived exosomes promote recovery from traumatic brain injury via microglia/macrophages in rat[J]. Aging (Albany NY), 2020, 12(18): 18274-18296.ZHAO Y M, GAN Y X, XU G W, et al. MSCs-derived exosomes attenuate acute brain injury and inhibit microglial inflammation by reversing cyslt2r-erk1/2 mediated microglia m1 polarization[J]. Neurochem Res, 2020, 45(5): 1180-1190.LI G Y, XIAO L H, QIN H, et al. Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion[J]. Cell Cycle, 2020, 19(9): 1022-1035.LIU X L, ZHANG M M, LIU H N, et al. Bone marrow mesenchymal stem cell-derived exosomes attenuate cerebral ischemia-reperfusion injury-induced neuroinflammation and pyroptosis by modulating microglia m1/m2 phenotypes[J]. Exp Neurol, 2021, 34(1): 113-127.DUAN S R, WANG F, CAO J W, et al. Exosomes derived from microrna-146a-5p-enriched bone marrow mesenchymal stem cells alleviate intracerebral hemorrhage by inhibiting neuronal apoptosis and microglial m1 polarization[J]. Drug Des Devel Ther, 2020, 14(5): 3143-3158.ZHANG M, WANG L, HUANG S, et al. Exosomes with high level of miR-181c from bone marrow-derived mesenchymal stem cells inhibit inflammation and apoptosis to alleviate spinal cord injury[J]. J Mol Histol, 2021, 52(2): 301-311.ZHAO C L, ZHOU X, QIU J, et al. Exosomes derived from bone marrow mesenchymal stem cells inhibit complement activation in rats with spinal cord injury[J]. Drug Des Devel Ther, 2019, 13(9): 3693-3704.TANG B, SONG M, XIE X, et al. Tumor necrosis factor-stimulated gene-6 (TSG-6) secreted by BMSCs regulates activated astrocytes by inhibiting NF-κB signaling pathway to ameliorate blood brain barrier damage after intracerebral hemorrhage[J]. Neurochem Res, 2021, 14(6): 273-281.LIU K, CAI G L, ZHUANG Z, et al. Interleukin-1β-treated mesenchymal stem cells inhibit inflammation in hippocampal astrocytes through exosome-activated Nrf-2 signaling[J]. Int J Nanomedicine, 2021, 16(5): 1423-1434.DENG Y M, CHEN D D, GAO F, et al. Exosomes derived from microRNA-138-5p-overexpressing bone marrow-derived mesenchymal stem cells confer neuroprotection to astrocytes following ischemic stroke via inhibition of lcn2[J]. J Biol Eng, 2019, 28(13): 71.NAKANO M, KUBOTA K, KOBAYASHI E, et al. Bone marrow-derived mesenchymal stem cells improve cognitive impairment in an alzheimer's disease model by increasing the expression of microrna-146a in hippocampus[J]. Sci Rep, 2020, 10(1): 107-122.WANG L, PEI S, HAN L L, et al. Mesenchymal stem cell-derived exosomes reduce A1 astrocytes via downregulation of phosphorylated NFκB P65 subunit in spinal cord injury[J]. Cell Physiol Biochem, 2018, 50(4): 1535-1559.KUBOTA K, NAKANO M, KOBAYASHI E, et al. An enriched environment prevents diabetes-induced cognitive impairment in rats by enhancing exosomal miR-146a secretion from endogenous bone marrow-derived mesenchymal stem cells[J]. PLoS One, 2018, 13(9): 204-252.XIN H, WANG F, LI Y, et al. Secondary release of exosomes from astrocytes contributes to the increase in neural plasticity and improvement of functional recovery after stroke in rats treated with exosomes harvested from microrna 133b-overexpressing multipotent mesenchymal stromal cells[J]. Cell Transplant, 2017, 26(2): 243-257.MAHMOUDI M, TAGHAVI-FARAHABADI M, NAMAKI S, et al. Exosomes derived from mesenchymal stem cells improved function and survival of neutrophils from severe congenital neutropenia patients in vitro[J]. Hum Immunol, 2019, 80(12): 990-998.ZHANG B, LAI R C, SIM W K, et al. Topical application of mesenchymal stem cell exosomes alleviates the imiquimod induced psoriasis-like inflammation[J]. Int J Mol Sci, 2021, 22(2): 201-210.LI Q C, LIANG Y, SU Z B. Prophylactic treatment with MSC-derived exosomes attenuates traumatic acute lung injury in rats[J]. Am J Physiol Lung Cell Mol Physiol, 2019, 316(6): L1107-L1117.崔舒悦, 丁晓玲, 丁刚. 间充质干细胞来源的外泌体对巨噬细胞的影响[J]. 生命的化学, 2020, 40(10): 1825-1832.冉凤英, 陈龙, 张斌强, 等. TLRs信号通路激活的MSCs外泌体对巨噬细胞极化的影响[J]. 中华细胞与干细胞杂志(电子版), 2018, 8(02): 65-71.MAEDEH A, AMENE S, NIMA R. Anti-inflammatory and m2 macrophage polarization-promoting effect of mesenchymal stem cell-derived exosomes[J]. International Immunopharmacology, 2021, 97: 107823.赵吉玲, 余国龙, 彭漪, 等. 间充质干细胞调控炎性巨噬细胞极化的机制研究进展[J]. 医学综述, 2021, 27(2): 209-213.付正伟, 王丽霞, 葛海燕. 间充质干细胞对Th17/Treg平衡的影响及与IBD的关系[J]. 中华细胞与干细胞杂志(电子版), 2018, 8(06): 373-378.郭礼妍, 赖沛龙, 耿素霞, 等. 人脐带间充质干细胞来源外泌体对Treg和TH17细胞的调节作用[J]. 中国实验血液学杂志, 2019, 27(1): 221-226.李伟伟, 李晓丰, 侯萍, 等. 人脐带间充质干细胞外泌体可抑制Th22细胞的表达及功能[J]. 中国组织工程研究, 2018, 22(29): 4657-4662.林颖, 胡锦章, 颛孙永勋, 等. 骨髓间充质干细胞外泌体调节哮喘小鼠Foxp3+ Treg/Th17的平衡[J]. 中国组织工程研究, 2018, 22(17): 2637-2643.曾宪海, 萧苑, 邓祖辉, 等. 人牙髓间充质干细胞外泌体对小鼠树突状细胞成熟和功能的抑制作用[J]. 中华微生物学和免疫学杂志, 2019, 39(7): 506-513.DEWITTE S F H, LUK F, SIERRA P J M, et al. Immunomodulation by therapeutic mesenchymal stromal cells (MSC) is triggered through phagocytosis of MSC by monocytic cells[J]. Stem Cells, 2018, 36(4): 602-615.