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中华脑血管病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (04) : 230 -235. doi: 10.11817/j.issn.1673-9248.2022.04.003

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间充质干细胞治疗缺血性脑卒中机制的研究进展
李鸣1, 孙艳荣2, 裴艳宏2, 闫军浩3,()   
  1. 1. 100191 北京大学基础医学院人体解剖学与组织胚胎学系;450000 郑州大学基础医学院人体解剖学系
    2. 100191 北京大学基础医学院人体解剖学与组织胚胎学系
    3. 100191 北京大学基础医学院人体解剖学与组织胚胎学系;100191 北京市磁共振成像设备与技术北京市重点实验
  • 收稿日期:2022-01-27 出版日期:2022-08-01
  • 通信作者: 闫军浩
  • 基金资助:
    北京市自然科学基金研究专题(Z200025)

Research progress in the mechanism of mesenchymal stem cells in the treatment of ischemic stroke

Ming Li1, Yanrong Sun2, Yanhong Pei2, Junhao Yan3,()   

  1. 1. Department of Human Anatomy, histology and embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Human Anatomy, School of basic Medical Sciences, Zhengzhou University, Zhengzhou 450000, China
    2. Department of Human Anatomy, histology and embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
    3. Department of Human Anatomy, histology and embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Beijing key Laboratory of Magnetic Resonance Imaging Equipment and Technology, Beijing 100191, China
  • Received:2022-01-27 Published:2022-08-01
  • Corresponding author: Junhao Yan
引用本文:

李鸣, 孙艳荣, 裴艳宏, 闫军浩. 间充质干细胞治疗缺血性脑卒中机制的研究进展[J/OL]. 中华脑血管病杂志(电子版), 2022, 16(04): 230-235.

Ming Li, Yanrong Sun, Yanhong Pei, Junhao Yan. Research progress in the mechanism of mesenchymal stem cells in the treatment of ischemic stroke[J/OL]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2022, 16(04): 230-235.

缺血性脑卒中(IS)是由于脑血管闭塞导致脑血液循环中断而引起的神经功能障碍,给大量患者带来了不同程度的残疾负担。目前,IS发病率、患病率和死亡率整体呈上升趋势,成为亟待解决的公共卫生问题。然而,IS的治疗手段有限,预后仍不满意。值得注意的是,间充质干细胞(MSC)因能够促进受损中枢神经系统的功能恢复,已经成为基础研究和临床研究的热点。本文汇总了MSC的来源和给药途径,重点回顾了MSC治疗IS机制的研究进展以及临床研究现状,旨在为后续MSC在IS中的临床治疗策略探索提供参考。

Ischemic stroke (IS) is a neurological disorder caused by cerebral vascular occlusion, which leads to the interruption of cerebral blood circulation. It brings varying degrees of disability burden to a large number of patients. At present, the incidence, prevalence, and mortality of IS are on the rise as a whole, which has become a public health problem to be solved urgently. However, the treatment of IS is limited, and the prognosis is unsatisfactory. It is worth noting that mesenchymal stem cells (MSCs) have become the focus of basic and clinical research because they are speculated to promote the functional recovery of the damaged central nervous system. This review summarizes the sources and administration routes of MSCs, and focuses on the research progress in the mechanism and the clinical research status of MSCs in the treatment of IS, in order to provide a reference for the further exploration of clinical treatment strategies of MSCs in IS.

1
Mathers CD, Boerma T, Ma Fat D. Global and regional causes of death [J]. Br Med Bull, 2009, 92: 7-32.
2
王亚楠, 吴思缈, 刘鸣. 中国脑卒中15年变化趋势和特点 [J]. 华西医学, 2021, 36(6): 803-807.
3
Guo Y, Peng Y, Zeng H, et al. Progress in mesenchymal stem cell therapy for ischemic stroke [J]. Stem Cells Int, 2021, 2021: 9923566.
4
Johnson J, Shojaee M, Mitchell Crow J, et al. From mesenchymal stromal cells to engineered extracellular vesicles: a new therapeutic paradigm [J]. Front Cell Dev Biol, 2021, 9: 705676.
5
Kapetanos K, Asimakopoulos D, Christodoulou N, et al. Chronological age affects MSC senescence in vitro-a systematic review [J]. Int J Mol Sci, 2021, 22(15): 7945.
6
Gancheva MR, Kremer KL, Gronthos S, et al. Using dental pulp stem cells for stroke therapy [J]. Front Neurol, 2019, 10: 422.
7
Wu T, Xu W, Chen H, et al. Comparison of the differentiation of dental pulp stem cells and periodontal ligament stem cells into neuron-like cells and their effects on focal cerebral ischemia [J]. Acta Biochim Biophys Sin (Shanghai), 2020, 52(9): 1016-1029.
8
Barzegar M, Wang Y, Eshaq RS, et al. Human placental mesenchymal stem cells improve stroke outcomes via extracellular vesicles-mediated preservation of cerebral blood flow [J]. EBioMedicine, 2021, 63: 103161.
9
Jin K, Sun Y, Xie L, et al. Comparison of ischemia-directed migration of neural precursor cells after intrastriatal, intraventricular, or intravenous transplantation in the rat [J]. Neurobiol Dis, 2005, 18(2): 366-374.
10
Fischer UM, Harting MT, Jimenez F, et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect [J]. Stem Cells Dev, 2009, 18(5): 683-692.
11
Ishizaka S, Horie N, Satoh K, et al. Intra-arterial cell transplantation provides timing-dependent cell distribution and functional recovery after stroke [J]. Stroke, 2013, 44(3): 720-726.
12
Du S, Guan J, Mao G, et al. Intra-arterial delivery of human bone marrow mesenchymal stem cells is a safe and effective way to treat cerebral ischemia in rats [J]. Cell Transplant, 2014, 23 Suppl 1: S73-S82.
13
Lim JY, Jeong CH, Jun JA, et al. Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia [J]. Stem Cell Res Ther, 2011, 2(5): 38.
14
Li YH, Feng L, Zhang GX, et al. Intranasal delivery of stem cells as therapy for central nervous system disease [J]. Exp Mol Pathol, 2015, 98(2): 145-151.
15
Dabrowska S, Andrzejewska A, Lukomska B, et al. Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles [J]. J Neuroinflammation, 2019, 16(1): 178.
16
Nakajima M, Nito C, Sowa K, et al. Mesenchymal stem cells overexpressing interleukin-10 promote neuroprotection in experimental acute ischemic stroke [J]. Mol Ther Methods Clin Dev, 2017, 6: 102-111.
17
Oh SH, Choi C, Noh JE, et al. Interleukin-1 receptor antagonist-mediated neuroprotection by umbilical cord-derived mesenchymal stromal cells following transplantation into a rodent stroke model [J]. Exp Mol Med, 2018, 50(4): 1-12.
18
Sarmah D, Kaur H, Saraf J, et al. Mitochondrial dysfunction in stroke: implications of stem cell therapy [J]. Transl Stroke Res, 2018. Online ahead of print.
19
Saraf J, Sarmah D, Vats K, et al. Intra-arterial stem cell therapy modulates neuronal calcineurin and confers neuroprotection after ischemic stroke [J]. Int J Neurosci, 2019, 129(10): 1039-1044.
20
He S, Wang L, Miao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha [J]. Cell, 2009, 137(6): 1100-1111.
21
Kong D, Zhu J, Liu Q, et al. Mesenchymal stem cells protect neurons against hypoxic-ischemic injury via inhibiting parthanatos, necroptosis, and apoptosis, but not autophagy [J]. Cell Mol Neurobiol, 2017, 37(2): 303-313.
22
Li Y, Chen J, Chen XG, et al. Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery [J]. Neurology, 2002, 59(4): 514-523.
23
Horita Y, Honmou O, Harada K, et al. Intravenous administration of glial cell line-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in the adult rat [J]. J Neurosci Res, 2006, 84(7): 1495-1504.
24
Chen J, Li Y, Katakowski M, et al. Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat [J]. J Neurosci Res, 2003, 73(6): 778-786.
25
Schäbitz WR, Steigleder T, Cooper-Kuhn CM, et al. Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis [J]. Stroke, 2007, 38(7): 2165-2172.
26
Nomura T, Honmou O, Harada K, et al. I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat [J]. Neuroscience, 2005, 136(1): 161-169.
27
Gao Q, Li Y, Shen L, et al. Bone marrow stromal cells reduce ischemia-induced astrocytic activation in vitro [J]. Neuroscience, 2008, 152(3): 646-655.
28
Shen LH, Li Y, Gao Q, et al. Down-regulation of neurocan expression in reactive astrocytes promotes axonal regeneration and facilitates the neurorestorative effects of bone marrow stromal cells in the ischemic rat brain [J]. Glia, 2008, 56(16): 1747-1754.
29
Shen LH, Li Y, Chen J, et al. One-year follow-up after bone marrow stromal cell treatment in middle-aged female rats with stroke [J]. Stroke, 2007, 38(7): 2150-2156.
30
Siconolfi LB, Seeds NW. Mice lacking tPA, uPA, or plasminogen genes showed delayed functional recovery after sciatic nerve crush [J]. J Neurosci, 2001, 21(12): 4348-4355.
31
Xin H, Li Y, Shen LH, et al. Increasing tPA activity in astrocytes induced by multipotent mesenchymal stromal cells facilitate neurite outgrowth after stroke in the mouse [J]. PLoS One, 2010, 5(2): e9027.
32
Krupinski J, Kaluza J, Kumar P, et al. Role of angiogenesis in patients with cerebral ischemic stroke [J]. Stroke, 1994, 25(9): 1794-1798.
33
Toyama K, Honmou O, Harada K, et al. Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells after cerebral ischemia [J]. Exp Neurol, 2009, 216(1): 47-55.
34
Liu K, Guo L, Zhou Z, et al. Mesenchymal stem cells transfer mitochondria into cerebral microvasculature and promote recovery from ischemic stroke [J]. Microvasc Res, 2019, 123: 74-80.
35
Zhang Y, Ma L, Su Y, et al. Hypoxia conditioning enhances neuroprotective effects of aged human bone marrow mesenchymal stem cell-derived conditioned medium against cerebral ischemia in vitro [J]. Brain Res, 2019, 1725: 146432.
36
Zhu J, Liu Q, Jiang Y, et al. Enhanced angiogenesis promoted by human umbilical mesenchymal stem cell transplantation in stroked mouse is Notch1 signaling associated [J]. Neuroscience, 2015, 290: 288-299.
37
Onda T, Honmou O, Harada K, et al. Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia [J]. J Cereb Blood Flow Metab, 2008, 28(2): 329-340.
38
Adibhatla RM, Hatcher JF. Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies [J]. CNS Neurol Disord Drug Targets, 2008, 7(3): 243-253.
39
Schnoor M, Parkos CA. Disassembly of endothelial and epithelial junctions during leukocyte transmigration [J]. Front Biosci, 2008, 13: 6638-6652.
40
Cheng Z, Wang L, Qu M, et al. Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice [J]. J Neuroinflammation, 2018, 15(1): 135.
41
Moon GJ, Sung JH, Kim DH, et al. Application of mesenchymal stem cell-derived extracellular vesicles for stroke: biodistribution and microRNA study [J]. Transl Stroke Res, 2019, 10(5): 509-521.
42
Mashouri L, Yousefi H, Aref AR, et al. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance [J]. Mol Cancer, 2019, 18(1): 75.
43
Guo S, Perets N, Betzer O, et al. Intranasal delivery of mesenchymal stem cell derived exosomes loaded with phosphatase and tensin homolog siRNA repairs complete spinal cord injury [J]. ACS Nano, 2019, 13(9): 10015-10028.
44
Zhao Y, Gan Y, Xu G, 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.
45
Bueno C, Martínez-Morga M, García-Bernal D, et al. Differentiation of human adult-derived stem cells towards a neural lineage involves a dedifferentiation event prior to differentiation to neural phenotypes [J]. Sci Rep, 2021, 11(1): 12034.
46
Radhakrishnan S, Trentz OA, Reddy MS, et al. In vitro transdifferentiation of human adipose tissue-derived stem cells to neural lineage cells - a stage-specific incidence [J]. Adipocyte, 2019, 8(1): 164-177.
47
Zhao LR, Duan WM, Reyes M, et al. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats [J]. Exp Neurol, 2002, 174(1): 11-20.
48
Vu Q, Xie K, Eckert M, et al. Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke [J]. Neurology, 2014, 82(14): 1277-1286.
59
Savitz SI, Yavagal D, Rappard G, et al. A phase 2 randomized, sham-controlled trial of internal carotid artery infusion of autologous bone marrow-derived ALD-401 cells in patients with recent stable ischemic stroke (recover-stroke) [J]. Circulation, 2019, 139(2): 192-205.
50
Jaillard A, Hommel M, Moisan A, et al. Autologous mesenchymal stem cells improve motor recovery in subacute ischemic stroke: a randomized clinical trial [J]. Transl Stroke Res, 2020, 11(5): 910-923.
51
Levy ML, Crawford JR, Dib N, et al. Phase I/II study of safety and preliminary efficacy of intravenous allogeneic mesenchymal stem cells in chronic stroke [J]. Stroke, 2019, 50(10): 2835-2841.
52
Steinberg GK, Kondziolka D, Wechsler LR, et al. Two-year safety and clinical outcomes in chronic ischemic stroke patients after implantation of modified bone marrow-derived mesenchymal stem cells (SB623): a phase 1/2a study [J]. J Neurosurg, 2018: 1-11.
53
Satani N, Cai C, Giridhar K, et al. World-wide efficacy of bone marrow derived mesenchymal stromal cells in preclinical ischemic stroke models: systematic review and meta-analysis [J]. Front Neurol, 2019, 10: 405.
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