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中华细胞与干细胞杂志(电子版) ›› 2021, Vol. 11 ›› Issue (04) : 251 -255. doi: 10.3877/cma.j.issn.2095-1221.2021.04.009

综述

间充质干细胞来源的细胞外囊泡治疗创伤性脑损伤的研究进展
周志鸿1, 彭立辉1   
  1. 1. 410003 长沙,湖南师范大学第二附属医院 (中国人民解放军联勤保障部队第 921 医院)神经外科 神经修复学湖南省重点实验室
  • 收稿日期:2021-01-27 出版日期:2021-08-01
  • 基金资助:
    湖南省重点领域研发项目(2020SK2102)

Research progress of extracellular vesicles derived from mesenchymal stem cells in the treatment of traumatic brain injury

Zhihong Zhou1, Lihui Peng1   

  1. 1. Hunan Key Laboratory of Neurorestoratology, Department of Neurosurgery, the Second Affiliated Hospital (the 921st Hospital of PLA), Hunan Normal University, Changsha 410003, China
  • Received:2021-01-27 Published:2021-08-01
引用本文:

周志鸿, 彭立辉. 间充质干细胞来源的细胞外囊泡治疗创伤性脑损伤的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2021, 11(04): 251-255.

Zhihong Zhou, Lihui Peng. Research progress of extracellular vesicles derived from mesenchymal stem cells in the treatment of traumatic brain injury[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2021, 11(04): 251-255.

创伤性脑损伤(TBI)是导致死亡和残疾的主要原因之一。随着干细胞治疗与再生医学的发展,间充质干细胞(MSCs)移植治疗TBI改善颅脑神经功能障碍成为可能。目前研究显示,MSCs的神经保护作用之一是基于分泌多种生物活性物质,其中细胞外囊泡(EVs)起到一定的治疗作用。MSC-EVs作用机制可能与神经保护,调节免疫应答,促进血管生成,增加神经发生、保护血脑屏障有关。本文主要介绍MSC-EVs在治疗TBI中的研究进展。

Traumatic brain injury (TBI) is one of the leading causes of death and disability. With the development of stem cell therapy and regenerative medicine, it is possible for mesenchymal stem cells (MSCs) transplantation to treat TBI and improve craniocerebral neurological dysfunction. Current studies have shown that one of the neuroprotective effects of MSCs is based on the secretion of a variety of bioactive substances, in which extracellular vesicles (EVs) play a certain therapeutic role. The mechanism of MSC-EVs may be related to neuroprotection, regulating immune response, promoting angiogenesis, increasing neurogenesis and protecting the blood-brain barrier. This article mainly introduces the research progress of MSC-EVs in the treatment of TBI.

表1 间充质干细胞分泌的细胞外囊泡microRNA作用机制
1
Jiang JY, Gao GY, Feng JF, et al. Traumatic brain injury in China[J]. Lancet Neurol, 2019, 18(3):286-295.
2
Gao G, Wu X, Feng J, et al. Clinical characteristics and outcomes in patients with traumatic brain injury in China: a prospective, multicentre, longitudinal, observational study[J]. Lancet Neurol, 2020, 19(8):670-677.
3
Akamatsu Y, Hanafy KA. Cell death and recovery in traumatic brain injury[J]. Neurotherapeutics, 2020, 17(2):446-456.
4
Weiland A, Wang Y, Wu W, et al. Ferroptosis and its role in diverse brain diseases[J]. Mol Neurobiol, 2019, 56(7):4880-4893.
5
Delic V, Beck KD, Pang KCH, et al. Biological links between traumatic brain injury and Parkinson's disease[J]. Acta Neuropathol Commun, 2020, 8(1):45.
6
Gardner RC, Byers AL, Barnes DE, et al. Mild TBI and risk of Parkinson disease: A Chronic Effects of Neurotrauma Consortium Study[J]. Neurology, 2018, 90(20):e1771-e1779.
7
Gardner RC, Yaffe K. Epidemiology of mild traumatic brain injury and neurodegenerative disease[J]. Mol Cell Neurosci, 2015, 66(Pt B):75-80.
8
Mishra VK, Shih HH, Parveen F, et al. Identifying the therapeutic significance of mesenchymal stem cells[J]. Cells, 2020, 9(5):1145. doi: 10.3390/cells9051145.
9
Bang OY, Lee JS, Lee PH, et al. Autologous mesenchymal stem cell transplantation in stroke patients[J]. Ann Neurol, 2005, 57(6):874-882.
10
Zhang Y, Zhang Y, Chopp M, et al. Mesenchymal stem cell-derived exosomes improve functional recovery in rats after traumatic brain injury: a dose-response and therapeutic window study[J]. Neurorehabil Neural Repair, 2020, 34(7):616-626.
11
Harrell CR, Jovicic N, Djonov V, et al. Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases[J]. Cells, 2019, 8(12):1605. doi: 10.3390/cells8121605.
12
Zhao Y, Gan Y, Xu G, et al. Exosomes from MSCs overexpressing microRNA-223-3p attenuate cerebral ischemia through inhibiting microglial M1 polarization mediated inflammation[J]. Life Sci, 2020, 260:118403. doi: 10.1016/j.lfs.2020.118403.
13
Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, et al. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods[J]. J Cell Physiol, 2019, 234(5):5451-5465.
14
Qing L, Chen H, Tang J, et al. Exosomes and their MicroRNA Cargo: New Players in Peripheral Nerve Regeneration[J]. Neurorehabil Neural Repair, 2018, 32(9):765-776.
15
Yang Y, Ye Y, Kong C, et al. MiR-124 enriched exosomes promoted the M2 polarization of microglia and enhanced hippocampus neurogenesis after traumatic brain injury by inhibiting TLR4 pathway[J]. Neurochem Res, 2019, 44(4):811-828.
16
Xiao X, Jiang Y, Liang W, et al. miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2[J]. Mol Brain, 2019, 12(1):78. doi: 10.1186/s13041-019-0501-0.
17
Xin H, Katakowski M, Wang F, et al. MicroRNA cluster miR-17-92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats[J]. Stroke, 2017, 48(3):747-753.
18
Pan Q, Wang Y, Lan Q, et al. Exosomes derived from mesenchymal stem cells ameliorate hypoxia/reoxygenation-injured ecs via transferring microRNA-126[J]. Stem Cells Int, 2019, 2019:2831756. doi: 10.1155/2019/2831756.
19
Pan Q, Kuang X, Cai S, et al. miR-132-3p priming enhances the effects of mesenchymal stromal cell-derived exosomes on ameliorating brain ischemic injury[J]. Stem Cell Res Ther, 2020, 11(1):260. doi: 10.1186/s13287-020-01761-0.
20
Slater SC, Jover E, Martello A, et al. MicroRNA-532-5p Regulates Pericyte Function by Targeting the Transcription Regulator BACH1 and Angiopoietin-1[J]. Mol Ther, 2018, 26(12):2823-2837.
21
Cui GH, Wu J, Mou FF, et al. Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP/PS1 mice[J]. FASEB J, 2018, 32(2):654-668.
22
Williams AM, Dennahy IS, Bhatti UF, et al. Mesenchymal stem cell-derived exosomes provide neuroprotection and improve long-term neurologic outcomes in a swine model of traumatic brain injury and hemorrhagic shock[J]. J Neurotrauma, 2019, 36(1):54-60.
23
Huang X, Ding J, Li Y, et al. Exosomes derived from PEDF modified adipose-derived mesenchymal stem cells ameliorate cerebral ischemia-reperfusion injury by regulation of autophagy and apoptosis[J]. Exp Cell Res, 2018, 371(1):269-277.
24
Zhao M, Liu S, Wang C, et al. Mesenchymal stem cell-derived extracellular vesicles attenuate mitochondrial damage and inflammation by stabilizing mitochondrial DNA[J]. ACS Nano, 2021, 15(1):1519-1538.
25
Ni H, Yang S, Siaw-Debrah F, et al. Exosomes derived from bone mesenchymal stem cells ameliorate early inflammatory responses following traumatic brain injury[J]. Front Neurosci, 2019, 13:14. doi: 10.3389/fnins.2019.00014.
26
Chen Y, Li J, Ma B, 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.
27
Liu W, Rong Y, Wang J, et al. Exosome-shuttled miR 216a5p from hypoxic preconditioned mesenchymal stem cells repairtraumatic spinal cord injury by shifting microglial M1/M2 polarization[J]. J Neuroinflammation, 2020, 17(1):47. doi: 10.1186/s12974-020-1726-7.
28
Wu J, He J, Tian X, et al. microRNA-9-5p alleviates blood-brain barrier damage and neuroinflammation after traumatic brain injury[J]. J Neurochem, 2020, 153(6):710-726.
29
Weston NM, Rolfe AT, Freelin AH, et al. Traumatic brain injury modifies synaptic plasticity in newly-generated granule cells of the adult hippocampus[J]. Exp Neurol, 2021, 336:113527. doi: 10.1016/j.expneurol.2020.113527.
30
Ngwenya LB, Danzer SC. Impact of traumatic brain injury on neurogenesis[J]. Front Neurosci, 2019, 12:1014. doi: 10.3389/fnins.2018.01014.
31
Medalla M, Chang W, Calderazzo SM, et al. Treatment with mesenchymal-derived extracellular vesicles reduces injury-related pathology in pyramidal neurons of monkey perilesional ventral premotor cortex[J]. J Neurosci, 2020, 40(17):3385-3407.
32
Zhang Y, Chopp M, Meng Y, et al. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury[J]. J Neurosurg, 2015, 122(4):856-867.
33
Anderson JD, Johansson HJ, Graham CS, et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear Factor-KappaB signaling[J]. Stem Cells, 2016, 34(3):601-613.
34
Gonzalez-King H, García NA, Ontoria-Oviedo I, et al. Hypoxia inducible factor-1α potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes[J].Stem Cells, 2017, 35(7):1747-1759.
35
Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications[J]. Neurobiol Dis, 2004, 16(1):1-13.
36
Sorby-Adams AJ, Marcoionni AM, Dempsey ER, et al. The role of neurogenic inflammation in blood-brain barrier disruption and development of cerebral oedema following acute central nervous system (CNS) injury[J]. Int J Mol Sci, 2017, 18(8):1788. doi: 10.3390/ijms18081788.
37
van Vliet EA, Ndode-Ekane XE, Lehto LJ, et al. Long-lasting blood-brain barrier dysfunction and neuroinflammation after traumatic brain injury[J]. Neurobiol Dis, 2020, 145:105080. doi: 10.1016/j.nbd.2020.105080.
38
Chodobski A, Zink BJ, Szmydynger-Chodobska J. Blood-brain barrier pathophysiology in traumatic brain injury[J]. Transl Stroke Res, 2011, 2(4):492-516.
39
Turner RJ, Sharp FR. Implications of MMP9 for blood brain barrier disruption and hemorrhagic transformation following ischemic stroke[J].Front Cell Neurosci, 2016, 10:56. doi: 10.3389/fncel.2016.00056.
40
Ségaliny A, Riazifar M, Pham V, et al. Elucidation of exosome migration across the blood-brain barrier model in vitro[J]. Cell Mol Bioeng, 2016, 9(4):509-529.
41
Williams AM, Bhatti UF, Brown JF, et al. Early single-dose treatment with exosomes provides neuroprotection and improves blood-brain barrier integrity in swine model of traumatic brain injury and hemorrhagic shock[J]. J Trauma Acute Care Surg, 2020, 88(2):207-218.
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