间充质干细胞源外泌体在神经退行性疾病治疗中的应用与进展

doi:10.3877/cma.j.issn.2095-1221.2023.02.005

中华细胞与干细胞杂志(电子版) ›› 2023, Vol. 13 ›› Issue (02) : 93 -100. doi: 10.3877/cma.j.issn.2095-1221.2023.02.005

综述

间充质干细胞源外泌体在神经退行性疾病治疗中的应用与进展

雷双银, 习剑鑫, 贺羽轩, 姚静宜, 石博雅, 马杰, 池光范, 李美英^†(

)

130000　长春，吉林大学白求恩第二临床医学院
130000　长春，吉林大学白求恩第三临床医学院
130000　长春，吉林大学白求恩第一临床医学院
130000　长春，吉林大学药学院
130000　长春，吉林大学基础医学院病理生物学教育部重点实验室

收稿日期:2023-02-21 出版日期:2023-04-01
通信作者: 李美英
基金资助:
国家自然科学基金(82271425，81870974)

Applications and advances of mesenchymal stem cells-derived exosomes in treating neurodegenerative diseases

Shuangyin Lei, Jianxin Xi, Yuxuan He, Jingyi Yao, Boya Shi, Jie Ma, Guangfan Chi, Meiying Li^†()

Norman Bethune Second Clinical Medical College, Jilin University, Changchun 130000, China
Norman Bethune Third Clinical Medical College, Jilin University, Changchun 130000, China
Norman Bethune First Clinical Medical College, Jilin University, Changchun 130000, China
College of Pharmaceutical Sciences, Jilin University, Changchun 130000, China
The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Science, Jilin University, Changchun 130000, China

Received:2023-02-21 Published:2023-04-01
Corresponding author: Meiying Li

全文 ( ) 下载PDF ( ) 导出引用

引用本文：

雷双银, 习剑鑫, 贺羽轩, 姚静宜, 石博雅, 马杰, 池光范, 李美英. 间充质干细胞源外泌体在神经退行性疾病治疗中的应用与进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2023, 13(02): 93-100.

Shuangyin Lei, Jianxin Xi, Yuxuan He, Jingyi Yao, Boya Shi, Jie Ma, Guangfan Chi, Meiying Li. Applications and advances of mesenchymal stem cells-derived exosomes in treating neurodegenerative diseases[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(02): 93-100.

随着老龄化时代的到来，神经退行性疾病患者人数急剧上升。神经退行性疾病严重降低患者的生活质量和生命周期，目前世界范围内仍然缺乏有效的治疗手段。间充质干细胞源外泌体（MSC-exos）富含功能性生物活性物质，作为细胞间通讯的新途径，为神经退行性疾病的治疗开辟了全新方向。在临床前研究和临床研究中，该新型无细胞疗法在减轻神经炎症、抑制神经细胞死亡和诱导神经再生等方面显示出巨大潜力。此外，相比传统治疗，其具有易通过血脑屏障、高安全性和低免疫原性等多种优势。本文主要就MSC-exos治疗阿尔茨海默病、帕金森病和肌萎缩侧索硬化症等慢性神经退行性疾病的最新研究进行综述，并提出讨论与展望，以期推动MSC-exos在神经退行性疾病的基础研究和临床应用。

关键词: 神经退行性疾病, 间充质干细胞, 外泌体

With the advent of the aging era, the number of people suffering from neurodegenerative diseases has dramatically increased. Neurodegenerative diseases severely reduce the quality of life and life cycle of patients, and there is still a lack of effective treatments worldwide. Mesenchymal stem cells-derived exosomes (MSC-exos), rich in functional bioactive substances, have opened up a whole novel direction for treating neurodegenerative diseases as a new pathway for intercellular communication. This novel cell-free therapy has shown great potential in reducing neuroinflammation, inhibiting neural cell death, and inducing neural regeneration in preclinical and clinical studies. In addition, it has various advantages over conventional therapies, such as easy passage through the blood-brain barrier, high safety, and low immunogenicity. This review focuses on the latest research on MSC-exos for the treatment of chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. It presents a discussion and outlook to promote the basic research and clinical application of MSC-exos in neurodegenerative diseases.

Key words: Neurodegenerative diseases, Mesenchymal stem cells, Exosomes

表1 MSC-exos治疗AD的相关研究

组织来源	治疗细胞/动物	治疗方式	作用机制	治疗效应	参考文献
骨髓	APP/PS1小鼠	静脉注射	激活SphK/S1P信号通路，抑制Aβ沉积，增加NeuN表达	提高小鼠的空间学习和记忆能力	[25]
骨髓	APP/PS1小鼠及其原代培养神经元	脑室内注射	抑制Aβ诱导的iNOS表达	缓解突触损伤，改善了小鼠认知行为	[26]
骨髓	AD大鼠（通过在SD大鼠侧脑室注射Aβ建立）及AD体外细胞模型	侧脑室内注射	将miR-29c-3p递送至神经元，以抑制β-分泌酶表达并激活Wnt/β-catenin通路	减少Aβ沉积面积和斑块，增加体外AD海马神经元活力	[27]
骨髓	3xTg-AD小鼠	鼻内给药	促使小胶质细胞极化为抗炎表型并增加了树突棘密度	抑制小胶质细胞激活，调控神经炎症，发挥神经保护作用	[28]
骨髓	AD小鼠（通过在C57BL/6小鼠脑室注射STZ建立）	侧脑室注射	抑制海马区小胶质细胞和星形胶质细胞过度活化，下调促炎细胞因子表达，上调突触功能相关蛋白表达	减轻中枢神经系统炎症，改善注射STZ的小鼠的AD样行为	[29]
骨髓	海马神经元	—	抑制Aβ诱导的氧化应激和突触损伤	保护海马神经元免受Aβ的毒害	[30]
脐带	J20-AD小鼠及具有家族性AD突变的神经细胞培养模型	静脉注射	下调HDAC4表达，恢复突触可塑性相关基因表达	改善AD小鼠脑葡萄糖代谢和认知功能	[31]
脐带	APP/PS1小鼠	脑室内注射	减少Aβ水平、炎症反应和氧化应激，抑制小胶质细胞活化	改善小鼠空间学习能力和认知缺陷	[32]
脂肪	转基因小鼠衍生的AD体外模型	—	降低Aβ水平，增加促凋亡蛋白表达	改善Aβ诱导的神经元凋亡	[33]

表1 MSC-exos治疗AD的相关研究

组织来源	治疗细胞/动物	治疗方式	作用机制	治疗效应	参考文献
骨髓	APP/PS1小鼠	静脉注射	激活SphK/S1P信号通路，抑制Aβ沉积，增加NeuN表达	提高小鼠的空间学习和记忆能力	[25]
骨髓	APP/PS1小鼠及其原代培养神经元	脑室内注射	抑制Aβ诱导的iNOS表达	缓解突触损伤，改善了小鼠认知行为	[26]
骨髓	AD大鼠（通过在SD大鼠侧脑室注射Aβ建立）及AD体外细胞模型	侧脑室内注射	将miR-29c-3p递送至神经元，以抑制β-分泌酶表达并激活Wnt/β-catenin通路	减少Aβ沉积面积和斑块，增加体外AD海马神经元活力	[27]
骨髓	3xTg-AD小鼠	鼻内给药	促使小胶质细胞极化为抗炎表型并增加了树突棘密度	抑制小胶质细胞激活，调控神经炎症，发挥神经保护作用	[28]
骨髓	AD小鼠（通过在C57BL/6小鼠脑室注射STZ建立）	侧脑室注射	抑制海马区小胶质细胞和星形胶质细胞过度活化，下调促炎细胞因子表达，上调突触功能相关蛋白表达	减轻中枢神经系统炎症，改善注射STZ的小鼠的AD样行为	[29]
骨髓	海马神经元	—	抑制Aβ诱导的氧化应激和突触损伤	保护海马神经元免受Aβ的毒害	[30]
脐带	J20-AD小鼠及具有家族性AD突变的神经细胞培养模型	静脉注射	下调HDAC4表达，恢复突触可塑性相关基因表达	改善AD小鼠脑葡萄糖代谢和认知功能	[31]
脐带	APP/PS1小鼠	脑室内注射	减少Aβ水平、炎症反应和氧化应激，抑制小胶质细胞活化	改善小鼠空间学习能力和认知缺陷	[32]
脂肪	转基因小鼠衍生的AD体外模型	—	降低Aβ水平，增加促凋亡蛋白表达	改善Aβ诱导的神经元凋亡	[33]

表2 MSCs的分泌组（含Exos）治疗PD的相关研究

组织来源	治疗细胞/动物	治疗方式	作用机制	治疗效应	参考文献
骨髓	PD大鼠（通过在Wistar-Han雄性大鼠脑室注射6-OHDA建立）	黑质内纹状体给药	VEGF、BDNF、IL-6、GDNF和PEDF表达增多	部分恢复PD大鼠的运动表型和神经元结构	[46]
骨髓	6-OHDA刺激的PD体外细胞模型	—	稳定了生理α-syn单体，并减少了聚集的不溶性p-S129 α-syn，上调了Bax/Bcl-2的比例	减少鱼藤酮诱导的细胞死亡，促进神经再生	[47]
骨髓	α-syn诱导的线虫	—	减少α-syn聚集物的数量	减轻线虫多巴胺能神经变性，从而神经保护作用	[48]
骨髓	PD大鼠（通过在Wistar-Han雄性大鼠大鼠脑室注射6-OHDA建立）	静脉注射	UPS依赖性蛋白质平衡的恢复	减少多巴胺能神经元的死亡，恢复PD大鼠运动功能	[49]
骨髓	PD大鼠（通过在SD大鼠皮下注射鱼藤酮建立）	静脉注射	血清TGF-β1和MCP-1水平大幅下降，血清BDNF和脑多巴胺水平以及脑TH和巢蛋白基因表达显着升高	促进大鼠自体神经元再生和移植细胞分化为神经细胞，恢复纹状体组织结构完整	[50]
脐带	PD小鼠（通过在C57BL/6小鼠腹膜内注射MPTP建立）	静脉注射	抑制NLRP3炎症小体在中枢和外周器官中的表达	抑制黑质中小胶质细胞活化，减轻了神经炎症，缓解了小鼠的PD样行为	[51]
脂肪	促氧化剂（H₂O₂）和6-OHDA处理的人神经母细胞瘤SH-SY5Y细胞	—	上调SIRT3水平	减少ROS生成，减弱氧化应激，起到神经保护作用	[52]

表2 MSCs的分泌组（含Exos）治疗PD的相关研究

组织来源	治疗细胞/动物	治疗方式	作用机制	治疗效应	参考文献
骨髓	PD大鼠（通过在Wistar-Han雄性大鼠脑室注射6-OHDA建立）	黑质内纹状体给药	VEGF、BDNF、IL-6、GDNF和PEDF表达增多	部分恢复PD大鼠的运动表型和神经元结构	[46]
骨髓	6-OHDA刺激的PD体外细胞模型	—	稳定了生理α-syn单体，并减少了聚集的不溶性p-S129 α-syn，上调了Bax/Bcl-2的比例	减少鱼藤酮诱导的细胞死亡，促进神经再生	[47]
骨髓	α-syn诱导的线虫	—	减少α-syn聚集物的数量	减轻线虫多巴胺能神经变性，从而神经保护作用	[48]
骨髓	PD大鼠（通过在Wistar-Han雄性大鼠大鼠脑室注射6-OHDA建立）	静脉注射	UPS依赖性蛋白质平衡的恢复	减少多巴胺能神经元的死亡，恢复PD大鼠运动功能	[49]
骨髓	PD大鼠（通过在SD大鼠皮下注射鱼藤酮建立）	静脉注射	血清TGF-β1和MCP-1水平大幅下降，血清BDNF和脑多巴胺水平以及脑TH和巢蛋白基因表达显着升高	促进大鼠自体神经元再生和移植细胞分化为神经细胞，恢复纹状体组织结构完整	[50]
脐带	PD小鼠（通过在C57BL/6小鼠腹膜内注射MPTP建立）	静脉注射	抑制NLRP3炎症小体在中枢和外周器官中的表达	抑制黑质中小胶质细胞活化，减轻了神经炎症，缓解了小鼠的PD样行为	[51]
脂肪	促氧化剂（H₂O₂）和6-OHDA处理的人神经母细胞瘤SH-SY5Y细胞	—	上调SIRT3水平	减少ROS生成，减弱氧化应激，起到神经保护作用	[52]

1	Andreone BJ, Larhammar M, Lewcock JW. Cell death and neurodegeneration[J]. Cold Spring Harb Perspect Biol, 2020, 12(2):a036434. doi: 10.1101/cshperspect.a036434.
2	Staff NP, Jones DT, Singer W. Mesenchymal stromal cell therapies for neurodegenerative diseases[J]. Mayo Clin Proc, 2019, 94(5):892-905.
3	Chen X, Pan W. The treatment strategies for neurodegenerative diseases by integrative medicine[J]. Integr Med Int, 2014, 1(4):223-225.
4	Sadatpoor SO, Salehi Z, Rahban D, et al. Manipulated mesenchymal stem cells applications in neurodegenerative diseases[J]. Int J Stem Cells, 2020, 13(1):24-45.
5	Yuan O, Lin C, Wagner J, et al. Exosomes derived from human primed mesenchymal stem cells induce mitosis and potentiate growth factor secretion[J]. Stem Cells Dev, 2019, 28(6):398-409.
6	Fayazi N, Sheykhhasan M, Soleimani Asl S, et al. Stem cell-derived exosomes: a new strategy of neurodegenerative disease treatment[J]. Molecular neurobiology, 2021, 58(7):3494-34514.
7	Witwer KW, Van Balkom BWM, Bruno S, et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications[J]. J Extracell Vesicles, 2019, 8(1):1609206. doi: 10.1080/20013078.2019.1609206.
8	Pegtel DM, Gould SJ. Exosomes[J]. Annu Rev Biochem, 2019, 88:487-514.
9	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.
10	Guo M, Yin Z, Chen F, et al. Mesenchymal stem cell-derived exosome: a promising alternative in the therapy of Alzheimer's disease[J]. Alzheimers Res Ther, 2020, 12(1):109.doi: 10.1186/s13195-020-00670-x.
11	Bagno L, Hatzistergos KE, Balkan W, et al. Mesenchymal stem cell-based therapy for cardiovascular disease: progress and challenges[J]. Mol Ther, 2018, 26(7):1610-1623.
12	Hedayat M, Ahmadi M, Shoaran M, et al. Therapeutic application of mesenchymal stem cells derived exosomes in neurodegenerative diseases: a focus on non-coding RNAs cargo, drug delivery potential, perspective[J]. Life Sci, 2023, 320:121566. doi: 10.1016/j.lfs.2023.121566.
13	2020 Alzheimer's disease facts and figures[J]. Alzheimers Dement, 2020. doi: 10.1002/alz.12068.
14	Lane CA, Hardy J, Schott JM. Alzheimer's disease[J]. Eur J Neurol, 2018, 25(1):59-70.
15	Long JM, Holtzman DM. Alzheimer disease: an update on pathobiology and treatment strategies[J]. Cell, 2019, 179(2):312-339.
16	de Dios C, Bartolessis I, Roca-Agujetas V, et al. Oxidative inactivation of amyloid beta-degrading proteases by cholesterol-enhanced mitochondrial stress[J]. Redox Biol, 2019, 26:101283. doi: 10.1016/j.redox.2019.101283.
17	Katsuda T, Tsuchiya R, Kosaka N, et al. Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes[J]. Sci Rep, 2013, 3:1197.doi: 10.1038/srep01197.
18	Xiong WP, Yao WQ, Wang B, et al. BMSCs-exosomes containing GDF-15 alleviated SH-SY5Y cell injury model of Alzheimer's disease via AKT/GSK-3β/β-catenin[J]. Brain Res Bull, 2021, 177:92-102.
19	Ding M, Shen Y, Wang P, et al. Exosomes isolated from human umbilical cord mesenchymal stem cells alleviate neuroinflammation and reduce amyloid-beta deposition by modulating microglial activation in Alzheimer's disease[J]. Neurochem Res, 2018, 43(11):2165-2177.
20	Pascoal TA, Benedet AL, Ashton NJ, et al. Microglial activation and tau propagate jointly across Braak stages[J]. Nat Med, 2021, 27(9):1592-1599.
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	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):10772. doi: 10.1038/s41598-020-67460-1.
23	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. doi: 10.1161/STROKEAHA.116.015204.
24	Wei H, Xu Y, Chen Q, et al. Mesenchymal stem cell-derived exosomal miR-223 regulates neuronal cell apoptosis[J]. Cell Death Dis, 2020, 11(4):290.doi: 10.1038/s41419-020-2490-4.
25	Wang X, Yang G. Bone marrow mesenchymal stem cells-derived exosomes reduce Aβ deposition and improve cognitive function recovery in mice with Alzheimer's disease by activating sphingosine kinase/sphingosine-1-phosphate signaling pathway[J]. Cell Biol Int, 2021, 45(4):775-784.
26	Wang SS, Jia J,Wang Z. Mesenchymal stem cell-derived extracellular vesicles suppresses iNOS expression and ameliorates neural impairment in Alzheimer's disease mice[J]. J Alzheimers Dis, 2018, 61(3):1005-1013.
27	Sha S, Shen X, Cao Y, et al. Mesenchymal stem cells-derived extracellular vesicles ameliorate Alzheimer's disease in rat models via the microRNA-29c-3p/BACE1 axis and the Wnt/β-catenin pathway[J]. Aging (Albany NY), 2021, 13(11):15285-306.
28	Losurdo M, Pedrazzoli M, D'Agostino C, et al. Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer's disease[J]. Stem Cells Transl Med, 2020, 9(9):1068-1084.
29	Liu S, Fan M, Xu JX, et al. Exosomes derived from bone-marrow mesenchymal stem cells alleviate cognitive decline in AD-like mice by improving BDNF-related neuropathology[J]. J Neuroinflammation, 2022, 19(1):35.doi: 10.1186/s12974-022-02393-2.
30	de Godoy MA, Saraiva LM, de Carvalho LRP, et al. Mesenchymal stem cells and cell-derived extracellular vesicles protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers[J]. J Biol Chem, 2018, 293(6):1957-1975.
31	Chen YA, Lu CH, Ke CC, et al. Mesenchymal stem cell-derived exosomes ameliorate Alzheimer's disease pathology and improve cognitive deficits[J]. Biomedicines, 2021, 9(6):594. doi: 10.3390/biomedicines9060594.
32	Yang L, Zhai Y, Hao Y, et al. The regulatory functionality of exosomes derived from hUMSCs in 3D culture for Alzheimer's disease therapy[J]. Small, 2020, 16(3):e1906273.doi: 10.1002/smll.201906273.
33	Lee M, Ban JJ, Yang S, et al. The exosome of adipose-derived stem cells reduces β-amyloid pathology and apoptosis of neuronal cells derived from the transgenic mouse model of Alzheimer's disease[J]. Brain Res, 2018, 1691:87-93.
34	Zayed MA, Sultan S, Alsaab HO, et al. Stem-cell-based therapy: the celestial weapon against neurological disorders[J]. Cells, 2022, 11(21):3476. doi: 10.3390/cells11213476.
35	Zheng Y, Zhou J, Wang Y, et al. Neural stem/progenitor cell transplantation in Parkinson's rodent animals: a meta-analysis and systematic review[J]. Stem Cells Transl Med, 2022, 11(4):383-393.
36	Rodríguez-Pallares J, García-Garrote M, Parga JA, et al. Combined cell-based therapy strategies for the treatment of Parkinson's disease: focus on mesenchymal stromal cells[J]. Neural Regen Res, 2023, 18(3):478-484.
37	Jarmalavičiūtė A, Tunaitis V, Pivoraitė U, et al. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis[J]. Cytotherapy, 2015, 17(7):932-939.
38	Teixeira FG, Vilaça-Faria H, Domingues AV, et al. Preclinical comparison of stem cells secretome and levodopa application in a 6-Hydroxydopamine rat model of Parkinson's disease[J]. Cells, 2020, 9(2):315. doi: 10.3390/cells9020315.
39	Chen HX, Liang FC, Gu P, et al. Exosomes derived from mesenchymal stem cells repair a Parkinson's disease model by inducing autophagy[J]. Cell Death Dis, 2020, 11(4):288. doi: 10.1038/s41419-020-2473-5.
40	Li Q, Wang Z, Xing H, et al. Exosomes derived from miR-188-3p-modified adipose-derived mesenchymal stem cells protect Parkinson's disease[J]. Mol Ther Nucleic Acids, 2021, 23:1334-1344.
41	Xue C, Li X, Ba L, et al. MSC-derived exosomes can enhance the angiogenesis of human brain MECs and show therapeutic potential in a mouse model of Parkinson's disease[J]. Aging Dis, 2021, 12(5):1211-1222.
42	Lee HK, Finniss S, Cazacu S, et al. Mesenchymal stem cells deliver exogenous miRNAs to neural cells and induce their differentiation and glutamate transporter expression[J]. Stem Cells Dev, 2014, 23(23):2851-2861.
43	Xin H, Li Y, Buller B, et al. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth[J]. Stem Cells, 2012, 30(7):1556-1564.
44	Lopez-Verrilli MA, Caviedes A, Cabrera A, et al. Mesenchymal stem cell-derived exosomes from different sources selectively promote neuritic outgrowth[J]. Neuroscience, 2016, 320:129-139.
45	Sun Z, Gu P, Xu H, et al. Human umbilical cord mesenchymal stem cells improve locomotor function in Parkinson's disease mouse model through regulating intestinal microorganisms[J]. Front Cell Dev Biol, 2022, 9:808905. doi: 10.3389/fcell.2021.808905.
46	Teixeira FG, Carvalho MM, Panchalingam KM, et al. Impact of the secretome of human mesenchymal stem cells on brain structure and animal behavior in a rat model of Parkinson's disease[J]. Stem Cells Transl Med, 2017, 6(2):634-646.
47	Ramalingam M, Jang S, Jeong HS. Therapeutic effects of conditioned medium of neural differentiated human bone marrow-derived stem cells on rotenone-induced alpha-synuclein aggregation and apoptosis[J]. Stem Cells Int, 2021, 2021:6658271. doi: 10.1155/2021/6658271.
48	Marques CR, Pereira-Sousa J, Teixeira FG, et al. Mesenchymal stem cell secretome protects against alpha-synuclein-induced neurodegeneration in a caenorhabditis elegans model of Parkinson's disease[J]. Cytotherapy, 2021, 23(10):894-901.
49	Mendes-Pinheiro B, Anjo SI, Manadas B, et al. Bone marrow mesenchymal stem cells' secretome exerts neuroprotective effects in a Parkinson's disease rat model[J]. Front Bioeng Biotechnol, 2019, 7:294.doi: 10.3389/fbioe.2019.00294.
50	Ahmed HH, Salem AM, Atta HM, et al. Updates in the pathophysiological mechanisms of Parkinson's disease: emerging role of bone marrow mesenchymal stem cells[J]. World J Stem Cells, 2016, 8(3):106-117.
51	Zhou L, Wang X, Wang X, et al. Neuroprotective effects of human umbilical cord mesenchymal stromal cells in PD mice via centrally and peripherally suppressing NLRP3 inflammasome-mediated inflammatory responses[J]. Biomed Pharmacother, 2022, 153:113535. doi: 10.1016/j.biopha.2022.113535.
52	Chierchia A, Chirico N, Boeri L, et al. Secretome released from hydrogel-embedded adipose mesenchymal stem cells protects against the Parkinson's disease related toxin 6-hydroxydopamine[J]. Eur J Pharm Biopharm, 2017, 121:113-120.
53	Oskarsson B, Gendron TF, Staff NP. Amyotrophic lateral sclerosis: an update for 2018[J]. Mayo Clin Proc, 2018, 93(11):1617-1628.
54	Xu L, Liu T, Liu L, et al. Global variation in prevalence and incidence of amyotrophic lateral sclerosis: a systematic review and meta-analysis[J]. J Neurol, 2020, 267(4):944-953.
55	Fang MY, Markmiller S, Vu AQ, et al. Small-molecule modulation of TDP-43 recruitment to stress granules prevents persistent TDP-43 accumulation in ALS/FTD[J]. Neuron, 2019, 103(5):802-19.e11.
56	Deora V, Lee JD, Albornoz EA, et al. The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins[J]. Glia, 2020, 68(2):407-421.
57	Giunti D, Marini C, Parodi B, et al. Role of miRNAs shuttled by mesenchymal stem cell-derived small extracellular vesicles in modulating neuroinflammation[J]. Sci Rep, 2021, 11(1):1740. doi: 10.1038/s41598-021-81039-4.
58	Wang X, Zhang Y, Jin T, et al. Adipose-derived mesenchymal stem cells combined with extracellular vesicles may improve amyotrophic lateral sclerosis[J]. Front Aging Neurosci, 2022, 14:830346.doi: 10.3389/fnagi.2022.830346.
59	Zuo X, Zhou J, Li Y, et al. TDP-43 aggregation induced by oxidative stress causes global mitochondrial imbalance in ALS[J]. Nat Struct Mol Biol, 2021, 28(2):132-142.
60	Bonafede R, Scambi I, Peroni D, et al. Exosome derived from murine adipose-derived stromal cells: neuroprotective effect on in vitro model of amyotrophic lateral sclerosis[J]. Exp Cell Res, 2016, 340(1):150-158.
61	Calabria E, Scambi I, Bonafede R, et al. ASCs-exosomes recover coupling efficiency and mitochondrial membrane potential in an in vitro model of ALS[J]. Front Neurosci, 2019, 13:1070.doi: 10.3389/fnins.2019.01070.
62	Bonafede R, Brandi J, Manfredi M, et al. The anti-apoptotic effect of ASC-Exosomes in an in vitro ALS model and their proteomic analysis[J]. Cells, 2019, 8(9):1087. doi: 10.3390/cells8091087.
63	Bonafede R, Turano E, Scambi I, et al. ASC-exosomes ameliorate the disease progression in SOD1(G93A) murine model underlining their potential therapeutic use in human ALS[J]. Int J Mol Sci, 2020, 21(10):3651. doi: 10.3390/ijms21103651.
64	Soundara Rajan T, Giacoppo S, Diomede F, et al. Human periodontal ligament stem cells secretome from multiple sclerosis patients suppresses NALP3 inflammasome activation in experimental autoimmune encephalomyelitis[J]. Int J Immunopathol Pharmacol, 2017, 30(3):238-252.
65	Li Z, Liu F, He X, et al. Exosomes derived from mesenchymal stem cells attenuate inflammation and demyelination of the central nervous system in EAE rats by regulating the polarization of microglia[J]. Int Immunopharmacol, 2019, 67:268-280.
66	Zhang J, Buller BA, Zhang ZG, et al. Exosomes derived from bone marrow mesenchymal stromal cells promote remyelination and reduce neuroinflammation in the demyelinating central nervous system[J]. Exp Neurol, 2022, 347:113895. doi: 10.1016/j.expneurol.2021.113895.
67	Park KR, Hwang CJ, Yun HM, et al. Prevention of multiple system atrophy using human bone marrow-derived mesenchymal stem cells by reducing polyamine and cholesterol-induced neural damages[J]. Stem Cell Res Ther, 2020, 11(1):63.doi: 10.1186/s13287-020-01590-1.
68	Wenceslau CV, de Souza DM, Mambelli-Lisboa NC, et al. Restoration of BDNF, DARPP32, and D2R expression following intravenous infusion of human immature dental pulp stem cells in Huntington's disease 3-NP rat model[J]. Cells, 2022, 11(10):1664. doi: 10.3390/cells11101664.
69	Giampà C, Alvino A, Magatti M, et al. Conditioned medium from amniotic cells protects striatal degeneration and ameliorates motor deficits in the R6/2 mouse model of Huntington's disease[J]. J Cell Mol Med, 2019, 23(2):1581-1592.
70	Bashyal S, Thapa C, Lee S. Recent progresses in exosome-based systems for targeted drug delivery to the brain[J]. J Control Release, 2022, 348:723-744.
71	SHARMA S, MASUD M K, KANETI Y V, et al. Extracellular vesicle nanoarchitectonics for novel drug delivery applications[J]. Small, 2021, 17(42):e2102220.doi: 10.1002/smll.202102220.
72	Jahangard Y, Monfared H, Moradi A, et al. Therapeutic effects of transplanted exosomes containing miR-29b to a rat model of Alzheimer's disease[J]. Front Neurosci, 2020, 14:564-564. doi: 10.3389/fnins.2020.00564.
73	Shi J, Jiang X, Gao S, et al. Gene-modified exosomes protect the brain against prolonged deep hypothermic circulatory arrest[J]. Ann Thorac Surg, 2021, 111(2):576-585.
74	Yang J, Luo S, Zhang J, et al. Exosome-mediated delivery of antisense oligonucleotides targeting α-synuclein ameliorates the pathology in a mouse model of Parkinson's disease[J]. Neurobiol Dis, 2021, 148:105218.doi: 10.1016/j.nbd.2020.105218.
75	Cui GH, Guo HD, Li H, et al. RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer's disease[J]. Immun Ageing, 2019, 16(1):10-10.doi: 10.1186/s12979-019-0150-2.
76	Liu L, Li Y, Peng H, et al. Targeted exosome coating gene-chem nanocomplex as "nanoscavenger" for clearing α-synuclein and immune activation of Parkinson's disease[J]. Sci Adv, 2020, 6(50):eaba3967. doi: 10.1126/sciadv.aba3967.
77	Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes[J]. Science, 2020, 367(6478):eaau6977. doi: 10.1126/science.aau6977.
78	Lai JJ, Chau ZL, Chen SY, et al. Exosome processing and characterization approaches for research and technology development[J]. Adv Sci (Weinh), 2022, 9(15):e2103222.doi: 10.1002/advs.202103222.
79	Guy R, Offen D. Promising opportunities for treating neurodegenerative diseases with mesenchymal stem cell-derived exosomes[J]. Biomolecules, 2020, 10(9):1320. doi: 10.3390/biom10091320.
80	Chen YS, Lin EY, Chiou TW, et al. Exosomes in clinical trial and their production in compliance with good manufacturing practice[J]. Ci Ji Yi Xue Za Zhi, 2020, 32(2):113-120.
81	Chu M, Wang H, Bian L, et al. Nebulization therapy with umbilical cord mesenchymal stem cell-derived exosomes for COVID-19 pneumonia[J]. Stem Cell Rev Rep, 2022, 18(6):2152-2163.
82	Mendt M, Rezvani K, Shpall E. Mesenchymal stem cell-derived exosomes for clinical use[J]. Bone Marrow Transplant, 2019, 54(Suppl 2):789-792.
83	Xunian Z, Kalluri R. Biology and therapeutic potential of mesenchymal stem cell-derived exosomes[J]. Cancer Sci, 2020, 111(9):3100-3110.
84	Malekian F, Shamsian A, Kodam SP, et al. Exosome engineering for efficient and targeted drug delivery: current status and future perspective[J]. J Physiol, 2022. doi: 10.1113/JP282799.
85	Xu M, Feng T, Liu B, et al. Engineered exosomes: desirable target-tracking characteristics for cerebrovascular and neurodegenerative disease therapies[J]. Theranostics, 2021, 11(18):8926-8944.

[1]	刘政宏, 袁春銮. 乳腺癌患者血清外泌体中长链非编码RNA BC200的表达及临床意义[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(04): 212-216.
[2]	林琳, 田思萌, 于永华, 徐飞飞, 黄明莉. 干细胞及其外泌体治疗宫腔黏连的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(03): 271-275.
[3]	刘昌玲, 张金丽, 张志, 李孝建, 汤文彬, 胡逸萍, 陈宾, 谢晓娜. 负载人脂肪干细胞外泌体的甲基丙烯酰化明胶水凝胶对人皮肤成纤维细胞增殖和迁移的影响[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(06): 517-525.
[4]	宋勤琴, 李双汝, 李林, 杜鹃, 刘继松. 间充质干细胞源性外泌体在改善病理性瘢痕中作用的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(06): 550-553.
[5]	曹胜军, 李全, 符雪, 邵天喜, 周延华. 人脂肪间充质干细胞多层膜片对促进裸鼠皮肤缺损愈合的效果观察[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(04): 341-347.
[6]	蔡定钦, 孙建国, 陈旭. 外泌体非编码RNAs与肺癌放射治疗的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 655-658.
[7]	傅红兴, 王植楷, 谢贵林, 蔡娟娟, 杨威, 严盛. 间充质干细胞促进胰岛移植效果的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 351-360.
[8]	王大伟, 陆雅斐, 皇甫少华, 陈玉婷, 陈澳, 江滨. 间充质干细胞通过调控免疫机制促进创面愈合的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 361-366.
[9]	袁园园, 岳乐淇, 张华兴, 武艳, 李全海. 间充质干细胞在呼吸系统疾病模型中肺组织分布及治疗机制的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 374-381.
[10]	王俊楠, 刘晔, 李若涵, 叶青松. 间充质干细胞调控肠脑轴治疗神经系统疾病的潜力[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(05): 313-319.
[11]	袁雨涵, 杨盛力. 体液和组织蛋白质组学分析在肝癌早期分子诊断中的研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 883-888.
[12]	仝心语, 谭凯, 白亮亮, 杜锡林. 外泌体在肝细胞癌诊疗中的应用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 384-388.
[13]	季鹏程, 鄂一民, 陆晨, 喻春钊. 循环外泌体相关生物标志物在结直肠癌诊断中的研究进展[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(04): 265-273.
[14]	辛强, 朱文豪, 何川, 李文臣, 陈勃, 王海峰. 神经胶质细胞来源的外泌体miRNAs对创伤性颅脑损伤后神经炎症的影响[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(03): 169-173.
[15]	汪鹏飞, 程莹莹, 赵海康. 骨髓间充质干细胞改善神经病理性疼痛的机制探讨[J/OL]. 中华脑科疾病与康复杂志(电子版), 2024, 14(04): 230-234.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Applications and advances of mesenchymal stem cells-derived exosomes in treating neurodegenerative diseases

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Applications and advances of mesenchymal stem cells-derived exosomes in treating neurodegenerative diseases