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

细胞外囊泡在肝移植中的应用进展

贾德功 贾志兴 郭珊珊 程颖

贾德功, 贾志兴, 郭珊珊, 等. 细胞外囊泡在肝移植中的应用进展[J]. 器官移植, 2021, 12(4): 477-483. doi: 10.3969/j.issn.1674-7445.2021.04.016
引用本文: 贾德功, 贾志兴, 郭珊珊, 等. 细胞外囊泡在肝移植中的应用进展[J]. 器官移植, 2021, 12(4): 477-483. doi: 10.3969/j.issn.1674-7445.2021.04.016
Jia Degong, Jia Zhixing, Guo Shanshan, et al. Application progress of extracellular vesicle in liver transplantation[J]. ORGAN TRANSPLANTATION, 2021, 12(4): 477-483. doi: 10.3969/j.issn.1674-7445.2021.04.016
Citation: Jia Degong, Jia Zhixing, Guo Shanshan, et al. Application progress of extracellular vesicle in liver transplantation[J]. ORGAN TRANSPLANTATION, 2021, 12(4): 477-483. doi: 10.3969/j.issn.1674-7445.2021.04.016

细胞外囊泡在肝移植中的应用进展

doi: 10.3969/j.issn.1674-7445.2021.04.016
基金项目: 

河南省医学科技攻关计划联合共建项目 LHGJ20200507

新乡医学院第一附属医院青年培育基金项目 QN-2019-B05

详细信息
    作者简介:

    贾德功,男,1992年生,硕士,住院医师,研究方向为器官移植,Email:jdgqimeng@foxmail.com

    通讯作者:

    程颖,女,1975年生,博士,研究员,研究方向为器官移植,Email:chengying75@sina.com

  • 中图分类号: R617, R392.4

Application progress of extracellular vesicle in liver transplantation

More Information
  • 摘要: 肝移植是治疗终末期肝病的有效方法,而肝缺血-再灌注损伤(IRI)和排斥反应大大降低了移植肝的存活率。因此,急需一种既可以减轻肝IRI又可以促进同种异体移植物免疫耐受的新方法,以提高移植肝的存活率。细胞外囊泡(EV)是由细胞释放到细胞外微环境的纳米颗粒,可以通过修复自噬、免疫抑制和促进组织再生减轻移植物损伤。这使得EV成为肝移植领域的研究热点,但其临床应用面临着众多挑战,如EV的分离、纯化、鉴定、储存以及如何靶向递送到目标细胞等。本文对EV在肝IRI中的作用机制、EV临床应用面临的挑战及EV的潜在应用进行综述,旨在为EV在肝移植的临床应用提供参考。

     

  • [1] TONIUTTO P, BITETTO D, FORNASIERE E, et al. Challenges and future developments in liver transplantation[J]. Minerva Gastroenterol Dietol, 2019, 65(2): 136-152. DOI: 10.23736/S1121-421X.18.02529-1.
    [2] MERION RM, SCHAUBEL DE, DYKSTRA DM, et al. The survival benefit of liver transplantation[J]. Am J Transplant, 2005, 5(2): 307-313. DOI: 10.1111/j.1600-6143.2004.00703.x.
    [3] DAR WA, SULLIVAN E, BYNON JS, et al. Ischaemia reperfusion injury in liver transplantation: cellular and molecular mechanisms[J]. Liver Int, 2019, 39(5): 788-801. DOI: 10.1111/liv.14091.
    [4] ADAM R, KARAM V, CAILLIEZ V, et al. 2018 annual report of the European Liver Transplant Registry (ELTR) - 50-year evolution of liver transplantation[J]. Transpl Int, 2018, 31(12): 1293-1317. DOI: 10.1111/tri.13358.
    [5] RANA A, ACKAH RL, WEBB GJ, et al. No gains in long-term survival after liver transplantation over the past three decades[J]. Ann Surg, 2019, 269(1): 20-27. DOI: 10.1097/SLA.0000000000002650.
    [6] KALLURI R, LEBLEU VS. The biology, function, and biomedical applications of exosomes[J]. Science, 2020, 367(6478): eaau6977. DOI: 10.1126/science.aau6977.
    [7] 刘晓莉, 周林, 韩崇旭. 骨髓瘤诊断及预后评估的新标志物-胞外囊泡[J]. 实用医学杂志, 2021, 37(8): 1084-1087, 1092. DOI: 10.3969/j.issn.1006-5725.2021.08.025.

    LIU XL, ZHOU L, HAN CX. Extracellular vesicle, a new marker for diagnosis and prognosis of myeloma[J]. J Pract Med, 2021, 37(8): 1084-1087, 1092. DOI: 10.3969/j.issn.1006-5725.2021.08.025.
    [8] WITWER KW, THÉRY C. Extracellular vesicles or exosomes? on primacy, precision, and popularity influencing a choice of nomenclature[J]. J Extracell Vesicles, 2019, 8(1): 1648167. DOI: 10.1080/20013078.2019.1648167.
    [9] VAN NIEL G, D'ANGELO G, RAPOSO G. Shedding light on the cell biology of extracellular vesicles[J]. Nat Rev Mol Cell Biol, 2018, 19(4): 213-228. DOI: 10.1038/nrm.2017.125.
    [10] 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. DOI: 10.1159/000480533.
    [11] CHAROENVIRIYAKUL C, TAKAHASHI Y, MORISHITA M, et al. Cell type-specific and common characteristics of exosomes derived from mouse cell lines: yield, physicochemical properties, and pharmacokinetics[J]. Eur J Pharm Sci, 2017, 96: 316-322. DOI: 10.1016/j.ejps.2016.10.009.
    [12] ALI M, PHAM A, WANG X, et al. Extracellular vesicles for treatment of solid organ ischemia-reperfusion injury[J]. Am J Transplant, 2020, 20(12): 3294-3307. DOI: 10.1111/ajt.16164.
    [13] XU Y, TANG Y, LU J, et al. PINK1-mediated mitophagy protects against hepatic ischemia/reperfusion injury by restraining NLRP3 inflammasome activation[J]. Free Radic Biol Med, 2020, 160: 871-886. DOI: 10.1016/j.freeradbiomed.2020.09.015.
    [14] SYRJÄ P, PALVIAINEN M, JOKINEN T, et al. Altered basal autophagy affects extracellular vesicle release in cells of Lagotto Romagnolo dogs with a variant ATG4D[J]. Vet Pathol, 2020, 57(6): 926-935. DOI: 10.1177/0300985820959243.
    [15] YANG B, DUAN W, WEI L, et al. Bone marrow mesenchymal stem cell-derived hepatocyte-like cell exosomes reduce hepatic ischemia/reperfusion injury by enhancing autophagy[J]. Stem Cells Dev, 2020, 29(6): 372-379. DOI: 10.1089/scd.2019.0194.
    [16] ZHANG L, SONG Y, CHEN L, et al. MiR-20a-containing exosomes from umbilical cord mesenchymal stem cells alleviates liver ischemia/reperfusion injury[J]. J Cell Physiol, 2020, 235(4): 3698-3710. DOI: 10.1002/jcp.29264.
    [17] YAO J, ZHENG J, CAI J, et al. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response[J]. FASEB J, 2019, 33(2): 1695-1710. DOI: 10.1096/fj.201800131RR.
    [18] SAFAKHEIL M, SAFAKHEIL H. The effect of exosomes derived from bone marrow stem cells in combination with rosuvastatin on functional recovery and neuroprotection in rats after ischemic stroke[J]. J Mol Neurosci, 2020, 70(5): 724-737. DOI: 10.1007/s12031-020-01483-1.
    [19] SUN CK, CHEN CH, CHANG CL, et al. Melatonin treatment enhances therapeutic effects of exosomes against acute liver ischemia-reperfusion injury[J]. Am J Transl Res, 2017, 9(4): 1543-1560. http://europepmc.org/abstract/MED/28469765
    [20] NONG K, WANG W, NIU X, et al. Hepatoprotective effect of exosomes from human-induced pluripotent stem cell-derived mesenchymal stromal cells against hepatic ischemia-reperfusion injury in rats[J]. Cytotherapy, 2016, 18(12): 1548-1559. DOI: 10.1016/j.jcyt.2016.08.002.
    [21] ZHENG L, LI Z, LING W, et al. Exosomes derived from dendritic cells attenuate liver injury by modulating the balance of Treg and Th17 cells after ischemia reperfusion[J]. Cell Physiol Biochem, 2018, 46(2): 740-756. DOI: 10.1159/000488733.
    [22] MA B, YANG JY, SONG WJ, et al. Combining exosomes derived from immature DCs with donor antigen-specific Treg cells induces tolerance in a rat liver allograft model[J]. Sci Rep, 2016, 6: 32971. DOI: 10.1038/srep32971.
    [23] HERRERA MB, FONSATO V, GATTI S, et al. Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats[J]. J Cell Mol Med, 2010, 14(6B): 1605-1618. DOI: 10.1111/j.1582-4934.2009.00860.x.
    [24] ANGER F, CAMARA M, ELLINGER E, et al. Human mesenchymal stromal cell-derived extracellular vesicles improve liver regeneration after ischemia reperfusion injury in mice[J]. Stem Cells Dev, 2019, 28(21): 1451-1462. DOI: 10.1089/scd.2019.0085.
    [25] NOJIMA H, FREEMAN CM, SCHUSTER RM, et al. Hepatocyte exosomes mediate liver repair and regeneration via sphingosine-1-phosphate[J]. J Hepatol, 2016, 64(1): 60-68. DOI: 10.1016/j.jhep.2015.07.030.
    [26] GARDINER C, DI VIZIO D, SAHOO S, et al. Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey[J]. J Extracell Vesicles, 2016, 5: 32945. DOI: 10.3402/jev.v5.32945.
    [27] COUMANS FAW, BRISSON AR, BUZAS EI, et al. Methodological guidelines to study extracellular vesicles[J]. Circ Res, 2017, 120(10): 1632-1648. DOI: 10.1161/CIRCRESAHA.117.309417.
    [28] NOCERA AL, MIYAKE MM, SEIFERT P, et al. Exosomes mediate interepithelial transfer of functional P-glycoprotein in chronic rhinosinusitis with nasal polyps[J]. Laryngoscope, 2017, 127(9): E295-E300. DOI: 10.1002/lary.26614.
    [29] GIMONA M, PACHLER K, LANER-PLAMBERGER S, et al. Manufacturing of human extracellular vesicle-based therapeutics for clinical use[J]. Int J Mol Sci, 2017, 18(6): 1190. DOI: 10.3390/ijms18061190.
    [30] DOYLE LM, WANG MZ. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis[J]. Cells, 2019, 8(7): 727. DOI: 10.3390/cells8070727.
    [31] KONOSHENKO MY, LEKCHNOV EA, VLASSOV AV, et al. Isolation of extracellular vesicles: general methodologies and latest trends[J]. Biomed Res Int, 2018: 8545347. DOI: 10.1155/2018/8545347.
    [32] GAO J, DONG X, WANG Z. Generation, purification and engineering of extracellular vesicles and their biomedical applications[J]. Methods, 2020, 177: 114-125. DOI: 10.1016/j.ymeth.2019.11.012.
    [33] PATEL DB, LUTHERS CR, LERMAN MJ, et al. Enhanced extracellular vesicle production and ethanol-mediated vascularization bioactivity via a 3D-printed scaffold-perfusion bioreactor system[J]. Acta Biomater, 2019, 95: 236-244. DOI: 10.1016/j.actbio.2018.11.024.
    [34] XIE H, WANG Z, ZHANG L, et al. Extracellular vesicle-functionalized decalcified bone matrix scaffolds with enhanced pro-angiogenic and pro-bone regeneration activities[J]. Sci Rep, 2017, 7: 45622. DOI: 10.1038/srep45622.
    [35] VAN DER POL E, STURK A, VAN LEEUWEN T, et al. Standardization of extracellular vesicle measurements by flow cytometry through vesicle diameter approximation[J]. J Thromb Haemost, 2018, 16(6): 1236-1245. DOI: 10.1111/jth.14009.
    [36] BARI E, DI SILVESTRE D, MASTRACCI L, et al. GMP-compliant sponge-like dressing containing MSC lyo-secretome: proteomic network of healing in a murine wound model[J]. Eur J Pharm Biopharm, 2020, 155: 37-48. DOI: 10.1016/j.ejpb.2020.08.003.
    [37] JEYARAM A, JAY SM. Preservation and storage stability of extracellular vesicles for therapeutic applications[J]. AAPS J, 2017, 20(1): 1. DOI: 10.1208/s12248-017-0160-y.
    [38] BROSSA A, FONSATO V, GRANGE C, et al. Extracellular vesicles from human liver stem cells inhibit renal cancer stem cell-derived tumor growth in vitro and in vivo[J]. Int J Cancer, 2020, 147(6): 1694-1706. DOI: 10.1002/ijc.32925.
    [39] MONROE MN, ZHAORIGETU S, GUPTA VS, et al. Extracellular vesicles influence the pulmonary arterial extracellular matrix in congenital diaphragmatic hernia[J]. Pediatr Pulmonol, 2020, 55(9): 2402-2411. DOI: 10.1002/ppul.24914.
    [40] LIU Z, WU C, ZOU X, et al. Exosomes derived from mesenchymal stem cells inhibit neointimal hyperplasia by activating the Erk1/2 signalling pathway in rats[J]. Stem Cell Res Ther, 2020, 11(1): 220. DOI: 10.1186/s13287-020-01676-w.
    [41] GU X, LI Y, CHEN K, et al. Exosomes derived from umbilical cord mesenchymal stem cells alleviate viral myocarditis through activating AMPK/mTOR-mediated autophagy flux pathway[J]. J Cell Mol Med, 2020, 24(13): 7515-7530. DOI: 10.1111/jcmm.15378.
    [42] LIU J, CHEN T, LEI P, et al. Exosomes released by bone marrow mesenchymal stem cells attenuate lung injury induced by intestinal ischemia reperfusion via the TLR4/NF-κB pathway[J]. Int J Med Sci, 2019, 16(9): 1238-1244. DOI: 10.7150/ijms.35369.
    [43] MAHDIPOUR E, SALMASI Z, SABETI N. Potential of stem cell-derived exosomes to regenerate β islets through Pdx-1 dependent mechanism in a rat model of type 1 diabetes[J]. J Cell Physiol, 2019, 234(11): 20310-20321. DOI: 10.1002/jcp.28631.
    [44] LIU Y, LOU G, LI A, et al. AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages[J]. EBioMedicine, 2018, 36: 140-150. DOI: 10.1016/j.ebiom.2018.08.054.
    [45] YANG J, LIU XX, FAN H, et al. Extracellular vesicles derived from bone marrow mesenchymal stem cells protect against experimental colitis via attenuating colon inflammation, oxidative stress and apoptosis[J]. PLoS One, 2015, 10(10): e0140551. DOI: 10.1371/journal.pone.0140551.
    [46] ZIPKIN M. Exosome redux[J]. Nat Biotechnol, 2019, 37(12): 1395-1400. DOI: 10.1038/s41587-019-0326-5.
    [47] EGGENHOFER E, BENSELER V, KROEMER A, et al. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion[J]. Front Immunol, 2012, 3: 297. DOI: 10.3389/fimmu.2012.00297.
    [48] SAMUELSSON E, SHEN H, BLANCO E, et al. Contribution of Kupffer cells to liposome accumulation in the liver[J]. Colloids Surf B Biointerfaces, 2017, 158: 356-362. DOI: 10.1016/j.colsurfb.2017.07.014.
    [49] MARTINS JP, DAS NEVES J, DE LA FUENTE M, et al. The solid progress of nanomedicine[J]. Drug Deliv Transl Res, 2020, 10(3): 726-729. DOI: 10.1007/s13346-020-00743-2.
    [50] KHALID A, PERSANO S, SHEN H, et al. Strategies for improving drug delivery: nanocarriers and microenvironmental priming[J]. Expert Opin Drug Deliv, 2017, 14(7): 865-877. DOI: 10.1080/17425247.2017.1243527.
    [51] GENTILE E, CILURZO F, DI MARZIO L, et al. Liposomal chemotherapeutics[J]. Future Oncol, 2013, 9(12): 1849-1859. DOI: 10.2217/fon.13.146.
    [52] BUSATTO S, WALKER SA, GRAYSON W, et al. Lipoprotein-based drug delivery[J]. Adv Drug Deliv Rev, 2020, 159: 377-390. DOI: 10.1016/j.addr.2020.08.003.
    [53] MAHMOUDIAN M, SALATIN S, KHOSROUSHAHI AY. Natural low- and high-density lipoproteins as mighty bio-nanocarriers for anticancer drug delivery[J]. Cancer Chemother Pharmacol, 2018, 82(3): 371-382. DOI: 10.1007/s00280-018-3626-4.
    [54] WOLFRAM J, FERRARI M. Clinical cancer nanomedicine[J]. Nano Today, 2019, 25: 85-98. DOI: 10.1016/j.nantod.2019.02.005.
    [55] ZHU X, BADAWI M, POMEROY S, et al. Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells[J]. J Extracell Vesicles, 2017, 6(1): 1324730. DOI: 10.1080/20013078.2017.1324730.
    [56] SCAVO MP, GENTILE E, WOLFRAM J, et al. Multistage vector delivery of sulindac and silymarin for prevention of colon cancer[J]. Colloids Surf B Biointerfaces, 2015, 136: 694-703. DOI: 10.1016/j.colsurfb.2015.10.005.
    [57] SHEN J, LIU H, MU C, et al. Multi-step encapsulation of chemotherapy and gene silencing agents in functionalized mesoporous silica nanoparticles[J]. Nanoscale, 2017, 9(16): 5329-5341. DOI: 10.1039/c7nr00377c.
    [58] TARDI P, JOHNSTONE S, HARASYM N, et al. In vivo maintenance of synergistic cytarabine: daunorubicin ratios greatly enhances therapeutic efficacy[J]. Leuk Res, 2009, 33(1): 129-139. DOI: 10.1016/j.leukres.2008.06.028.
  • 加载中
图(1)
计量
  • 文章访问数:  165
  • HTML全文浏览量:  19
  • PDF下载量:  12
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-04-24
  • 网络出版日期:  2021-07-13
  • 刊出日期:  2021-07-15

目录

    /

    返回文章
    返回