中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

间充质干细胞及其外泌体治疗自身免疫性肝炎的研究进展

罗龙龙 王丽菲 郑英 李斌 卢利霞 李初谊 于晓辉 张久聪

引用本文:
Citation:

间充质干细胞及其外泌体治疗自身免疫性肝炎的研究进展

DOI: 10.3969/j.issn.1001-5256.2023.12.025
基金项目: 

甘肃省非感染性肝病临床医学研究中心 (21JR7RA017);

联勤保障部队第九四〇医院基金临床医学肝病诊治中心 (2021yxky079);

甘肃省科技计划项目任务书 (22YF7FA105);

甘肃省卫生健康行业科研计划项目合同书 (GSWSKY2021-054)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:罗龙龙负责检索文献,撰写论文;王丽菲、郑英、李斌、卢利霞、李初谊参与修改论文;于晓辉、张久聪负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    李斌, 2312115338@qq.com (ORCID: 0000-0002-8626-7624)

    张久聪, zhangjiucong@163.com (ORCID: 0000-0003-4006-3033)

Research advances in mesenchymal stem cells and their exosomes in treatment of autoimmune hepatitis

Research funding: 

Gansu Clinical Medical Research Center for Non-infectious Liver Diseases (21JR7RA017);

Liver Disease Diagnosis and Treatment Center, 940th Hospital Foundation, Joint Logistics Support Force (2021yxky079);

Gansu Province Science and Technology Plan Project Assignment (22YF7FA105);

Gansu Province Health Industry Scientific Research Plan Project Contract (GSWSKY2021-054)

More Information
  • 摘要: 自身免疫性肝炎(AIH)是由自身免疫系统攻击肝细胞所致的慢性肝炎,其慢性进展可能会导致肝硬化甚至肝细胞癌的发生。目前,针对AIH的治疗主要包括药物治疗和肝移植,但均存在着各自的局限性,这使得患者的临床获益有限。因此,寻找新的治疗药物和方法成为了当前亟待解决的关键问题。近年来研究表明,间充质干细胞及其外泌体可通过抑制炎症反应、增强肝细胞的再生、调节免疫系统等方式改善AIH患者的症状,在AIH治疗中具有广阔的应用前景。本文通过回顾已有文献,对间充质干细胞及其外泌体治疗AIH的机制和应用进展进行综述,以期为AIH的临床治疗提供新的思路。

     

  • 图  1  AIH的发病机制

    注: APC,抗原呈递细胞;CTL,细胞毒性T淋巴细胞。

    Figure  1.  The pathogenesis of AIH

    图  2  MSC移植治疗AIH的作用机制

    注: STAT,信号转导和转录激活因子;IL-35-MSC,IL-35基因修饰的MSC。

    Figure  2.  Mechanism of action of MSC transplantation for AIH

  • [1] CARDON A, CONCHON S, RENAND A. Mechanisms of autoimmune hepatitis[J]. Curr Opin Gastroenterol, 2021, 37( 2): 79- 85. DOI: 10.1097/MOG.0000000000000704.
    [2] DALEKOS GN, SAMAKIDOU A, LYBEROPOULOU A, et al. Recent advances in the diagnosis and management of autoimmune hepatitis[J]. Pol Arch Intern Med, 2022, 132( 9): 16334. DOI: 10.20452/pamw.16334.
    [3] OLIVAS I, RODRÍGUEZ-TAJES S, LONDOÑO MC. Autoimmune hepatitis: Challenges and novelties[J]. Med Clin, 2022, 159( 6): 289- 298. DOI: 10.1016/j.medcli.2022.04.004.
    [4] HU CX, WU ZW, LI LJ. Mesenchymal stromal cells promote liver regeneration through regulation of immune cells[J]. Int J Biol Sci, 2020, 16( 5): 893- 903. DOI: 10.7150/ijbs.39725.
    [5] HADE MD, SUIRE CN, SUO ZC. Mesenchymal stem cell-derived exosomes: Applications in regenerative medicine[J]. Cells, 2021, 10( 8): 1959. DOI: 10.3390/cells10081959.
    [6] CAI H, GUO HD. Mesenchymal stem cells and their exocytotic vesicles[J]. Int J Mol Sci, 2023, 24( 3): 2085. DOI: 10.3390/ijms24032085.
    [7] JIANG W, XU JY. Immune modulation by mesenchymal stem cells[J]. Cell Prolif, 2020, 53( 1): e12712. DOI: 10.1111/cpr.12712.
    [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] HARRELL CR, DJONOV V, VOLAREVIC V. The cross-talk between mesenchymal stem cells and immune cells in tissue repair and regeneration[J]. Int J Mol Sci, 2021, 22( 5): 2472. DOI: 10.3390/ijms22052472.
    [10] LIU JX, GAO JF, LIANG ZX, et al. Mesenchymal stem cells and their microenvironment[J]. Stem Cell Res Ther, 2022, 13( 1): 429. DOI: 10.1186/s13287-022-02985-y.
    [11] KALLURI R, LEBLEU VS. The biology, function, and biomedical applications of exosomes[J]. Science, 2020, 367( 6478): eaau6977. DOI: 10.1126/science.aau6977.
    [12] LAKSHMI KAVYA ANV, SUBRAMANIAN S, RAMAKRISHNA S. Therapeutic applications of exosomes in various diseases: A review[J]. Biomater Adv, 2022, 134: 112579. DOI: 10.1016/j.msec.2021.112579.
    [13] ZHOU XN, KALLURI R. Biology and therapeutic potential of mesenchymal stem cell-derived exosomes[J]. Cancer Sci, 2020, 111( 9): 3100- 3110. DOI: 10.1111/cas.14563.
    [14] LEI YG, YAO J, ZHENG J, et al. Human umbilical cord mesenchymal stem cel-derived extracellular vesicles enhance the recenerative capability of fibrotic liver[J]. Organ Transplant, 2023, 14( 3): 379- 388. DOI: 10.3969/j.issn.1674-7445.2023.03.009.

    雷耘果, 姚嘉, 郑俊, 等. 人脐带间充质干细胞来源的细胞外囊泡增强纤维化肝脏再生能力[J]. 器官移植, 2023, 14( 3): 379- 388. DOI: 10.3969/j.issn.1674-7445.2023.03.009.
    [15] JIANG LR, ZHANG SQ, HU HZ, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acute liver failure by reducing the activity of the NLRP3 inflammasome in macrophages[J]. Biochem Biophys Res Commun, 2019, 508( 3): 735- 741. DOI: 10.1016/j.bbrc.2018.11.189.
    [16] RONG XL, LIU JZ, YAO X, et al. Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/β-catenin pathway[J]. Stem Cell Res Ther, 2019, 10( 1): 98. DOI: 10.1186/s13287-019-1204-2.
    [17] TERZIROLI BERETTA-PICCOLI B, MIELI-VERGANI G, VERGANI D. Autoimmmune hepatitis[J]. Cell Mol Immunol, 2022, 19( 2): 158- 176. DOI: 10.1038/s41423-021-00768-8.
    [18] BOVENSIEPEN CS, SCHAKAT M, SEBODE M, et al. TNF-producing Th1 cells are selectively expanded in liver infiltrates of patients with autoimmune hepatitis[J]. J Immunol, 2019, 203( 12): 3148- 3156. DOI: 10.4049/jimmunol.1900124.
    [19] DI GIORGIO A, VERGANI D, MIELI-VERGANI G. Cutting edge issues in juvenile sclerosing cholangitis[J]. Dig Liver Dis, 2022, 54( 4): 417- 427. DOI: 10.1016/j.dld.2021.06.028.
    [20] HE Y, HWANG S, AHMED YA, et al. Immunopathobiology and therapeutic targets related to cytokines in liver diseases[J]. Cell Mol Immunol, 2021, 18( 1): 18- 37. DOI: 10.1038/s41423-020-00580-w.
    [21] EGGENHUIZEN PJ, NG BH, OOI JD. Treg enhancing therapies to treat autoimmune diseases[J]. Int J Mol Sci, 2020, 21( 19): 7015. DOI: 10.3390/ijms21197015.
    [22] ZHANG WQ, LIU X, ZHU YC, et al. Transcriptional and posttranslational regulation of Th17/Treg balance in health and disease[J]. Eur J Immunol, 2021, 51( 9): 2137- 2150. DOI: 10.1002/eji.202048794.
    [23] BEHAIRY BE, EL-ARABY HA, KADER HH ABD EL, et al. Assessment of intrahepatic regulatory T cells in children with autoimmune hepatitis[J]. Ann Hepatol, 2016, 15( 5): 682- 690. DOI: 10.5604/16652681.1212319.
    [24] DIESTELHORST J, JUNGE N, SCHLUE J, et al. Pediatric autoimmune hepatitis shows a disproportionate decline of regulatory T cells in the liver and of IL-2 in the blood of patients undergoing therapy[J]. PLoS One, 2017, 12( 7): e0181107. DOI: 10.1371/journal.pone.0181107.
    [25] KIMURA N, YAMAGIWA S, SUGANO T, et al. Possible involvement of chemokine C-C receptor 7- programmed cell death-1+ follicular helper T-cell subset in the pathogenesis of autoimmune hepatitis[J]. J Gastroenterol Hepatol, 2018, 33( 1): 298- 306. DOI: 10.1111/jgh.13844.
    [26] HE CM, YANG YL, ZHENG KY, et al. Mesenchymal stem cell-based treatment in autoimmune liver diseases: Underlying roles, advantages and challenges[J]. Ther Adv Chronic Dis, 2021, 12: 2040622321993442. DOI: 10.1177/2040622321993442.
    [27] CHEN Y, CHEN S, LIU LY, et al. Mesenchymal stem cells ameliorate experimental autoimmune hepatitis by activation of the programmed death 1 pathway[J]. Immunol Lett, 2014, 162( 2 Pt B): 222- 228. DOI: 10.1016/j.imlet.2014.10.021.
    [28] KIM JY, PARK M, KIM YH, et al. Tonsil-derived mesenchymal stem cells(T-MSCs) prevent Th17-mediated autoimmune response via regulation of the programmed death-1/programmed death ligand-1(PD-1/PD-L1) pathway[J]. J Tissue Eng Regen Med, 2018, 12( 2): e1022- e1033. DOI: 10.1002/term.2423.
    [29] XU F, FEI ZY, DAI HX, et al. Mesenchymal stem cell-derived extracellular vesicles with high PD-L1 expression for autoimmune diseases treatment[J]. Adv Mater, 2022, 34( 1): e2106265. DOI: 10.1002/adma.202106265.
    [30] GU YZ, XUE Q, CHEN YJ, et al. Different roles of PD-L1 and FasL in immunomodulation mediated by human placenta-derived mesenchymal stem cells[J]. Hum Immunol, 2013, 74( 3): 267- 276. DOI: 10.1016/j.humimm.2012.12.011.
    [31] YANG LL, JIA SN, SHAO X, et al. Interleukin-35 modulates the balance between viral specific CD4+CD25+CD127dim/- regulatory T cells and T helper 17 cells in chronic hepatitis B virus infection[J]. Virol J, 2019, 16( 1): 48. DOI: 10.1186/s12985-019-1158-0.
    [32] WANG W, GUO H, LI HY, et al. Interleukin-35 gene-modified mesenchymal stem cells protect concanavalin A-induced fulminant hepatitis by decreasing the interferon gamma level[J]. Hum Gene Ther, 2018, 29( 2): 234- 241. DOI: 10.1089/hum.2017.171.
    [33] WANG K, SHI YJ, SONG ZL, et al. Regulatory effect of rat bone marrow mesenchymal stem cells on Treg/Th17 immune balance in vitro[J]. Mol Med Rep, 2020, 21( 5): 2123- 2130. DOI: 10.3892/mmr.2020.11019.
    [34] CHEN QH, WU F, LIU L, et al. Mesenchymal stem cells regulate the Th17/Treg cell balance partly through hepatocyte growth factor in vitro[J]. Stem Cell Res Ther, 2020, 11( 1): 91. DOI: 10.1186/s13287-020-01612-y.
    [35] LIU XX, REN SD, QU XB, et al. Mesenchymal stem cells inhibit Th17 cells differentiation via IFN-γ-mediated SOCS3 activation[J]. Immunol Res, 2015, 61( 3): 219- 229. DOI: 10.1007/s12026-014-8612-2.
    [36] KIM SH, JUNG J, CHO KJ, et al. Immunomodulatory effects of placenta-derived mesenchymal stem cells on T cells by regulation of FoxP3 expression[J]. Int J Stem Cells, 2018, 11( 2): 196- 204. DOI: 10.15283/ijsc18031.
    [37] MELIEF SM, SCHRAMA E, BRUGMAN MH, et al. Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages[J]. Stem Cells, 2013, 31( 9): 1980- 1991. DOI: 10.1002/stem.1432.
    [38] HEIDARI M, POUYA S, BAGHAEI K, et al. The immunomodulatory effects of adipose-derived mesenchymal stem cells and mesenchymal stem cells-conditioned medium in chronic colitis[J]. J Cell Physiol, 2018, 233( 11): 8754- 8766. DOI: 10.1002/jcp.26765.
    [39] SHEN ZW, HUANG W, LIU J, et al. Effects of mesenchymal stem cell-derived exosomes on autoimmune diseases[J]. Front Immunol, 2021, 12: 749192. DOI: 10.3389/fimmu.2021.749192.
    [40] LU FB, CHEN DZ, CHEN L, et al. Attenuation of experimental autoimmune hepatitis in mice with bone mesenchymal stem cell-derived exosomes carrying microRNA-223-3p[J]. Mol Cells, 2019, 42( 12): 906- 918. DOI: 10.14348/molcells.2019.2283.
    [41] ZHAO JW, LI Y, JIA RR, et al. Mesenchymal stem cells-derived exosomes as dexamethasone delivery vehicles for autoimmune hepatitis therapy[J]. Front Bioeng Biotechnol, 2021, 9: 650376. DOI: 10.3389/fbioe.2021.650376.
  • 加载中
图(2)
计量
  • 文章访问数:  348
  • HTML全文浏览量:  90
  • PDF下载量:  48
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-02-25
  • 录用日期:  2023-04-15
  • 出版日期:  2023-12-12
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回