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中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2020, Vol. 10 ›› Issue (05) : 292 -296. doi: 10.3877/cma.j.issn.2095-1221.2020.05.007

所属专题： 文献；

综述

间充质干细胞外泌体的研究进展
冉凤英1, 陈龙1, 罗丹1, 陈琴华2,†()   
  1. 1. 十堰　442008，湖北医药学院附属东风医院实验中心
    2. 十堰　442008，湖北医药学院附属东风医院实验中心；518101　深圳，深圳市宝安纯中医治疗医院药学部
  • 收稿日期:2020-02-12 出版日期:2020-10-01
  • 通信作者: 陈琴华
  • 基金资助:
    国家自然科学基金(81872509); 湖北医药学院研究生创新资助项目(YC2019021)

Research progress in exosomes of mesenchymal stem cells

Fengying Ran1, Long Chen1, Dan Luo1, Qinhua Chen2,†()   

  1. 1. Experimental Center of Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan 442008, China
    2. Experimental Center of Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan 442008, China; Department of Pharmaceutical, Shenzhen Baoan Authentic TCM Therapy Hospital, Shenzhen 518101, China
  • Received:2020-02-12 Published:2020-10-01
  • Corresponding author: Qinhua Chen
  • About author:
    Corresponding author: Chen Qinhua, Email:
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冉凤英, 陈龙, 罗丹, 陈琴华. 间充质干细胞外泌体的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2020, 10(05): 292-296.

Fengying Ran, Long Chen, Dan Luo, Qinhua Chen. Research progress in exosomes of mesenchymal stem cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2020, 10(05): 292-296.

间充质干细胞（MSCs）是一种来自于中胚层的多能干细胞，具有高度的自我更新及多向分化潜能，并在适宜的条件下具有诱导分化为肌细胞、软骨细胞、成骨细胞、成脂细胞等多种细胞的能力。MSCs不仅具有多向分化潜能，而且还具有免疫调节功能，可抑制多种免疫细胞的性能，调节免疫应答。近年来，研究发现，来源于MSCs的外泌体（MSCs-Exo）具有与MSCs相似的组织损伤修复和再生功能。外泌体（exosome）是多种细胞分泌的膜外小囊泡，直径30 ~ 200 nm，可以转运核酸、脂质和蛋白质，参与细胞间的信息交流。与MSCs相比，外泌体用于临床疾病的治疗更加稳定，体内同种异体给药后免疫排斥反应的可能性较低，并可为各种疾病提供替代疗法。MSCs-Exo逐渐成为新的研究热点，本文将对MSCs-Exo的生物学特性、免疫调节作用和在临床疾病治疗中的研究进行综述。

关键词: 间充质干细胞, 外泌体, 免疫调节

Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from mesoderm, which have high self-renewal and multi-directional differentiation potential as well as the ability to induce and differentiate into myocytes, chondrocytes, osteoblasts, adipocytes. MSCs have multi-directional differentiation potential, and can regulate immunity, inhibit many immune cells performance as well as regulate immune response. The recent study have found that exosomes derived from MSCs (MSCs-Exo) have tissue repair and reconstruction functions similar to MSCs. Exosomes are extracellular vesicles secreted by a variety of cells with a diameter of 30 - 200 nm, which can transport nucleic acids, lipids and proteins and participate in cell information exchange. Compared with MSCs, exosomes are more reliable in clinical treatment and immune rejection possibility is lower after allogeneic administration in vivo, thus it can serve as an alternative therapy. MSCs-Exo has gradually become a new research hotspot. In this paper, the biological characteristics, immune regulation mechanism and MSCs-Exo research progress are reviewed.

Key words: Mesenchymal stem cell, Exosome, Immunoregulation
1
Shi Y, Du L, Lin L, et al. Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targets[J]. Nat Rev Drug Discov, 2017, 16(1):35-52.
2
Sharma A. Role of stem cell derived exosomes in tumor biology[J]. Int J Cancer, 2018, 142(6):1086-1092.
3
张礼翼，仝彩玲，安珂, 等. 间充质干细胞在器官移植中发挥免疫抑制作用及机制探讨的研究进展[J]. 器官移植, 2019, 10(5):612-616.
4
Pacienza N, Lee RH, Bae EH, et al. In vitro macrophage assay predicts the in vivo anti-inflammatory potential of exosomes from human mesenchymal stromal cells[J]. Mol Ther Methods Clinl Dev, 2018, 13:67-76.
5
Cassano JM, Schnabel LV, Goodale MB, et al. Inflammatory licensed equine MSCs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment[J]. Stem Cell Res Ther, 2018, 9(1):82.
6
Lai RC, Yeo RW, Lim SK. Mesenchymal stem cell exosomes[J]. Semin Cell Dev Biol, 2015, 40:82-88.
7
Del Fattore A, Luciano R, Pascucci L, et al. Immunoregulatory effects of mesenchymal stem cell-derived extracellular vesicles on T lymphocytes[J]. Cell Transplant, 2015, 24(12):2615-2627.
8
Cheng L, Zhang K, Wu S, et al. Focus on mesenchymal stem cell-derived exosomes: opportunities and challenges in cell-free therapy[J]. Stem Cells Int, 2017:6305295.
9
Deng H, Sun C, Sun Y, et al. Lipid, protein, and MicroRNA composition within mesenchymal stem cell-derived exosomes[J]. Cell Reprogram, 2018, 20(3):178-186.
10
Vakhshiteh F, Atyabi F, Ostad SN. Mesenchymal stem cell exosomes:a two-edged sword in cancer herapy. Int J Nanomedicine, 2019,14:2847-2859.
11
Li P, Kaslan M, Lee SH, et al. Progress in exosome isolation techniques[J]. Theranostics, 2017, 7(3):789-804.
12
Hou R, Li Y, Sui Z, et al. Advances in exosome isolation methods and their applications in proteomic analysis of biological samples[J]. Anal Bioanal Chem, 2019, 411(21):5351-5361.
13
Peterson MF, Otoc N, Sethi JK, et al. Integrated systems for exosome investigation[J]. Methods, 2015, 87(4):31-45.
14
Hannafon BN, Trigoso YD, Calloway CL, et al. Plasma exosome microRNAs are indicative of breast cancer[J]. Breast Cancer Res, 2016, 18(1):90-104.
15
Arbelaiz A, Azkargorta M, Krawczyk M, et al. Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma[J]. Hepatology, 2017, 66(4):1125-1143.
16
Sunman H, Canpolat U, Yorgun H, et al. Association between reverse electrical remodeling and cardiac fibrosis markers in patients with cardiac resynchronization therapy[J]. Turk Kardiyol Dern Ars, 2018, 46(2):84-91.
17
Davies RT, Kim J, Jang SC, et al. Microfluidic filtration system to isolate extracellular vesicles from blood[J]. Lab on A Chip, 2012, 12(24):5202-5210.
18
Zhao Z, Yang Y, Zeng Y, et al. A microfluidic ExoSearch chip for multiplexed exosome detection towards blood-based ovarian cancer diagnosis[J]. Lab on A Chip, 2015, 16(3):489-496.
19
Liu F, Vermesh O, Mani V, et al. The exosome total isolation chip[J]. Acs Nano, 2017, 11(11):10712-10723.
20
Cheng Y, Zeng Q, Han Q, et al. Effect of pH, temperature and freezing-thawing on quantity changes and cellular uptake of exosomes[J]. Protein Cell, 2019, 10(4):295-299.
21
Park SJ, Jeon H, Yoo SM, et al. The effect of storage temperature on the biological activity of extracellular vesicles for the complement system[J]. In Vitro Cell Dev Biol Anim, 2018, 54(6):423-429.
22
Rao F, Zhang D, Fang T, et al. Exosomes from human gingiva-derived mesenchymal stem cells combined with biodegradable chitin conduits promote rat sciatic nerve regeneration[J]. Stem Cells Int, 2019, 2546367.
23
Abbaszadeh H, Ghorbani F, Derakhshani M, et al. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles: A novel therapeutic paradigm[J]. J Cell Physiol, 2020, 235(2):706-717.
24
Mokarizadeh A, Delirezh N, Morshedi A, et al. Microvesicles derived from mesenchymal stem cells: Potent organelles for induction of tolerogenic signaling[J]. Immunol Lett, 2012, 147(1-2):47-54.
25
Robbins PD, Morelli AE. Regulation of immune responses by extracellular vesicles[J]. Nat Rev Immunol, 2014, 14(3):195-208.
26
Zhang B, Yin Y, Lai RC, et al. Mesenchymal stem cells secrete immunologically active exosomes[J]. Stem Cells Dev, 2014, 23(11): 1233-1244.
27
Chen W, Huang Y, Han J, et al. Immunomodulatory effects of mesenchymal stromal cells-derived exosome[J]. Immunol Res, 2016, 64(4):831-840.
28
Seo Y, Kim HS, Hong IS. Stem Cell-derived extracellular vesicles as immunomodulatory therapeutics[J]. Stem Cells Int, 2019:5126156.
29
Lo Sicco C, Reverberi D, Balbi C, et al. Mesenchymal stem cell-derived extracellular vesicles as mediators of anti-inflammatory effects: endorsement of macrophage polarization[J]. Stem Cells Transl Med, 2017, 6(3):1018-1028.
30
Guoping Z, Ruoqiong H, Guanguan Q, et al. Mesenchymal stromal cell-derived extracellular vesicles: regenerative and immunomodulatory effects and potential applications in sepsis[J]. Cell Tissue Res, 2018, 374(1):1-15.
31
Yu, Fujita, Tsukasa, et al. Clinical application of mesenchymal stem cell-derived extracellular vesicle-based therapeutics for inflammatory lung diseases[J]. J Clin Med, 2018, 7(10):1-21.
32
Garo LP, Murugaiyan G. Contribution of MicroRNAs to autoimmune diseases[J]. Cell Mol Life Sci, 2016, 73(10):1-11.
33
Hu P, Yang Q, Wang Q, et al. Corrigendum to: 'Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration'[J]. Burns Trauma, 2020,8:tkaa007.
34
Malesevic M, Gutknecht D, Prell E, et al. Anti-inflammatory effects of extracellular cyclosporins are exclusively mediated by CD147[J]. J Med Chem, 2013, 56(18):7302-7311.
35
Monguió-Tortajada M, Roura S, Gálvez-Montón C, et al. Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine[J]. Theranostics, 2017, 7(2):270-284.
36
Yu B, Shao H, Su C, et al. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1[J]. Sci Rep, 2016, 6:34562.
37
Geiger A, Walker A, Nissen E. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice[J]. Biochem Biophys Res Commun, 2015, 467(2):303-309.
38
Li X, Liu L, Yang J, et al. Exosome derived from human umbilical cord mesenchymal stem cell mediates MiR-181c attenuating burn-induced excessive inflammation[J]. EBioMedicine, 2016, 8:72-82.
39
Qi J, Zhou Y, Jiao Z, et al. Exosomes derived from human bone mar-row mesenchymal stem cells promote tumor growth through hedgehog signaling pathway[J]. Cell Physiol Biochem, 2017, 42(6):2242-2254.
40
Vallabhaneni KC, Penfornis P, Dhule S, et al. Extracellular vesicles from bone marrow mesenchymal stem/stromal cells transport tumor regulatory microRNA, proteins, and metabolites[J]. Oncotarget, 2015, 6(7):4953-4967.
41
Lopatina T, Bruno S, Tetta C, et al. Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential[J]. Cell Commun Signal, 2014, 12(1):26-38.
42
Xin H, Li Y, Cui Y, et al. Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats[J]. J Cereb Blood Flow Metab, 2013, 33(11):1711-1715.
43
Wu S, Ju G-Q, Du T, et al. Microvesicles derived from human umbilical cord Wharton's jelly mesenchymal stem cells attenuate bladder tumor cell growth in vitro and in vivo[J]. PLoS One, 2013, 8(4):e61366.
44
Takahara K, Inamoto T, Ibuki N, et al. 245 microRNA-145 mediates the inhibitory effect of adipose-derived stem cells on androgen-independent prostate cancer[J]. Eur Urol Suppl, 2016, 15(3):e245.
45
Bruno S, Collino F, Deregibus MC, et al. Microvesicles derived from human bone marrow mesenchymal stem cells inhibit tumor growth[J]. Stem Cells Dev, 2012, 22(5):758-771.
46
Roccaro A M, Sacco A, Maiso P, et al. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression[J]. J Clin Invest, 2013, 123(4):1542-1555.
47
Bucan V, Vaslaitis D, Peck C-T, et al. Effect of exosomes from rat adipose-derived mesenchymal stem cells on neurite outgrowth and sciatic nerve regeneration after crushinjury[J]. Mol Neurobiol, 2019, 56(3):1812-1824.
48
Wei Z, Fan B, Ding H, et al. Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous system injury[J]. Mol Cell Biochem, 2019, 457(1-2):51-59.
49
Yang P, Cai L, Zhang G, et al. The role of the miR-17-92 cluster in neurogenesis and angiogenesis in the central nervous system of adults[J]. J Neurosci Res, 2017, 95(8):1574-1581.
50
Mao Q, Nguyen PD, Shanti RM, et al. Gingiva-derived mesenchymal stem cell-extracellular vesicles activate Schwann cell repair phenotype and promote nerve regeneration[J]. Tissue Engineering Part A, 2019, 25(11-12):887-900.
51
Huang X, Ding J, Li YF, 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.
52
Zhang S, Chuah SJ, Lai RC, et al. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity[J]. Biomaterials, 2018, 156:16-27.
53
Mei J, Hairong W, Mingming J, et al. Exosomes from MiR-30d-5p-ADSCs reverse acute ischemic stroke-induced, autophagy-mediated brain injury by promoting M2 microglial/macrophage polarization[J]. Cell Physiol Biochem, 2018, 47(2):864-878.
54
Du Y, Li D, Han C, et al. Exosomes from human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs) protect liver against hepatic ischemia/reperfusion injury via activating sphingosine kinase and sphingosine-1-phosphate signaling pathway[J]. Cell Physiol Biochem, 2017, 43(2):611-625.
55
Li T, Yan Y, Wang B, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis[J]. Stem Cells Dev, 2013, 22(6):845-54.
56
Hu C, Zhao L, Li L. Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases[J]. Stem Cell Res Ther, 2019, 10(1):199-212.
57
Caccioppo A, Franchin L, Grosso A, et al. Ischemia reperfusion injury: Mechanisms of damage/protection and novel strategies for cardiac recovery/regeneration[J]. Int J Mol Sci, 2019, 20(20):5024-5060.
58
Jia H, Liu W, Zhang B, et al. Enhanced autophagy via modulation of ATG16L in preventing cisplatin-induced acute kidney injury[J]. Am J Transl Res, 2018, 10(1):101-113.
59
Tsuji K, Kitamura S, Wada J, et al. Secretomes from mesenchymal stem cells against acute kidney injury: Possible heterogeneity[J]. Stem Cells Int, 2018:8693137.
60
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.
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