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Review | Open Access

The potential role of extracellular vesicles as hepatic diagnostic and therapeutic tools: Can the dream come true?

Tropical Medicine, Gastroenterology and Hepatology, Hepatoma Group, Faculty of Medicine, Ain Shams University, Cairo 11588, Egypt
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Abstract

Chronic liver disease of various aetiologies with underlying cirrhosis is a serious cause of liver-related morbidity and mortality globally. The emerging role of non-invasive diagnostic/therapeutic tools in different stages of liver disease represents a challenge and an area of great interest for many researchers, which could differ in the clinical outcome of liver disease patients. Over a decade, several studies have evaluated the emerging role of circulating extracellular vesicles (EVs) as biomarkers and therapeutic targets in different liver diseases; They are small membrane-encapsulated particles that can act as potent vehicles via their cargos between different hepatic cell types and also between organs, because of their ability to transfer proteins, lipids, and nucleic acids to affect the recipient cells' related physiological functions. Hence, the issues related to the potential use of EVs as biomarkers in liver disease diagnosis, prognosis, and even to assess the response to treatment, have been handled in our review concluding that EVs have shown promising results as potential diagnostic tools and for further evaluation as therapeutic targets.

References

[1]

Yáñez-Mó M, Siljander PRM, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 2015;4:27066. https://doi.org/10.3402/jev.v4.27066.

[2]

Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018;7(1):1535750. https://doi.org/10.1080/20013078.2018.1535750.

[3]

Kornek M, Lynch M, Mehta SH, et al. Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis. Gastroenterology 2012;143(2):448–58. https://doi.org/10.1053/j.gastro.2012.04.031.

[4]

Povero D, Yamashita H, Ren W, et al. Characterization and proteome of circulating extracellular vesicles as potential biomarkers for NASH. Hepatol Commun 2020; 4(9):1263–78. https://doi.org/10.1002/hep4.1556.

[5]

Li J, Liu H, Mauer AS, et al. Characterization of cellular sources and circulating levels of extracellular vesicles in a dietary murine model of nonalcoholic steatohepatitis. Hepatol Commun 2019;3(9):1235–49. https://doi.org/10.1002/hep4.1404.

[6]

Wu D, Zhu H, Wang H. Extracellular vesicles in non-alcoholic fatty liver disease and alcoholic liver disease. Front Physiol 2021;12:707429. https://doi.org/10.3389/fphys.2021.707429.

[7]

Momen-Heravi F, Bala, Kodys K, et al. Exosomes derived from alcohol-treated hepatocytes horizontally transfer liver specific miRNA-122 and sensitize monocytes to LPS. Sci Rep 2015;5: 9991. https://doi.org/10.1038/srep09991.

[8]

Lee JH, Shim YR, Seo W, et al. Mitochondrial double-stranded RNA in exosome promotes interleukin-17 production through toll-like receptor 3 in alcohol-associated liver injury. Hepatology 2020;72(2):609–25. https://doi.org/10.1002/hep.31041.

[9]

Brandon-Warner E, Feilen NA, Culberson CR, et al. Processing of miR17-92 cluster in hepatic stellate cells promotes hepatic fibrogenesis during alcohol-induced injury. Alcohol Clin Exp Res 2016;40(7):1430–42. https://doi.org/10.1111/acer.13116.

[10]

Cho YE, Mezey E, Hardwick JP, et al. Increased ethanol-inducible cytochrome P450-2E1 and cytochrome P450 isoforms in exosomes of alcohol-exposed rodents and patients with alcoholism through oxidative and endoplasmic reticulum stress. Hepatol Commun 2017;1(7):675–90. https://doi.org/10.1002/hep4.1066.

[11]

Sukriti S, Maras JS, Bihari C, et al. Microvesicles in hepatic and peripheral vein can predict nonresponse to corticosteroid therapy in severe alcoholic hepatitis. Aliment Pharmacol Ther 2018;47(8):1151–61. https://doi.org/10.1111/apt.14564.

[12]

Sehrawat TS, Arab JP, Liu M, et al. Circulating extracellular vesicles carrying sphingolipid cargo for the diagnosis and dynamic risk profiling of alcoholic hepatitis. Hepatology 2021;73(2):571–85. https://doi.org/10.1002/hep.31256.

[13]

Montaldo C, Terri M, Riccioni V, et al. Fibrogenic signals persist in DAA-treated HCV patients after sustained virological response. J Hepatol 2021;75(6):1301–11. https://doi.org/10.1016/j.jhep.2021.07.003.

[14]

Kornek M, Popov Y, Libermann TA, et al. Human T cell microparticles circulate in blood of hepatitis patients and induce fibrolytic activation of hepatic stellate cells. Hepatology 2011;53(1):230–42. https://doi.org/10.1002/hep.23999.

[15]

Kakizaki M, Yamamoto Y, Yabuta S, et al. The immunological function of extracellular vesicles in hepatitis B virus-infected hepatocytes. PLoS One 2018; 13(12):e0205886. https://doi.org/10.1371/journal.pone.0205886.

[16]

Seo W, Eun HS, Kim SY, et al. Exosome-mediated activation of toll-like receptor 3 in stellate cells stimulates interleukin-17 production by γδ T cells in liver fibrosis. Hepatology 2016;64(2):616–31. https://doi.org/10.1002/hep.28644.

[17]

Devaraj E, Perumal E, Subramaniyan R, et al. Liver fibrosis: extracellular vesicles mediated intercellular communication in perisinusoidal space. Hepatology 2022; 76(1):275–85. https://doi.org/10.1002/hep.32239.

[18]

Bruno S, Chiabotto G, Camussi G. Extracellular vesicles: a therapeutic option for liver fibrosis. Int J Mol Sci 2020;21(12):4255. https://doi.org/10.3390/ijms21124255.

[19]

Payancé A, Silva-Junior G, Bissonnette J, et al. Hepatocyte microvesicle levels improve prediction of mortality in patients with cirrhosis. Hepatology 2018;68(4):1508–18. https://doi.org/10.1002/hep.29903.

[20]

Julich-Haertel H, Urban SK, Krawczyk M, et al. Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma and hepatocellular carcinoma. J Hepatol 2017;67(2):282–92. https://doi.org/10.1016/j.jhep.2017.02.024.

[21]

Sun N, Zhang C, Lee YT, et al. HCC EV ECG score: an extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma. Hepatology 2023;77(3):774–88. https://doi.org/10.1002/hep.32692.

[22]

Wang Y, Zhang C, Zhang P, et al. Serum exosomal microRNAs combined with alpha-fetoprotein as diagnostic markers of hepatocellular carcinoma. Cancer Med 2018; 7(5):1670–9. https://doi.org/10.1002/cam4.1390.

[23]

Tian XP, Wang CY, Jin XH, et al. Acidic microenvironment up-regulates exosomal miR-21 and miR-10b in early-stage hepatocellular carcinoma to promote cancer cell proliferation and metastasis. Theranostics 2019;9(7):1965–79. https://doi.org/10.7150/thno.30958.

[24]

Wang C, Li N, Li Y, et al. Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy. J Nanobiotechnol 2022;20(1):247. https://doi.org/10.1186/s12951-022-01462-1.

[25]

Borrelli DA, Yankson K, Shukla N, et al. Extracellular vesicle therapeutics for liver disease. J Contr Release 2018;273:86–98. https://doi.org/10.1016/j.jconrel.2018.01.022.

[26]

Tang K, Zhang Y, Zhang H, et al. Delivery of chemotherapeutic drugs in tumour cell-derived microparticles. Nat Commun 2012;3:1282. https://doi.org/10.1038/ncomms2282.

[27]

Haga H, Yan IK, Takahashi K, et al. Extracellular vesicles from bone marrow-derived mesenchymal stem cells improve survival from lethal hepatic failure in mice. Stem Cells Transl Med 2017;6(4):1262–72. https://doi.org/10.1002/sctm.16-0226.

[28]

Rong X, Liu J, Yao X, et al. Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/β-catenin pathway. Stem Cell Res Ther 2019;10(1):98. https://doi.org/10.1186/s13287-019-1204-2.

[29]

Povero D, Pinatel EM, Leszczynska A, et al. Human induced pluripotent stem cell-derived extracellular vesicles reduce hepatic stellate cell activation and liver fibrosis. JCI Insight 2019;5(14):e125652. https://doi.org/10.1172/jci.insight.125652.

[30]

Bissonnette J, Altamirano J, Devue C, et al. A prospective study of the utility of plasma biomarkers to diagnose alcoholic hepatitis. Hepatology 2017;66(2):555–63. https://doi.org/10.1002/hep.29080.

[31]

van Niel G, D'Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018;19(4):213–28. https://doi.org/10.1038/nrm.2017.125.

[32]

van Niel G, Carter DRF, Clayton A, et al. Challenges and directions in studying cell-cell communication by extracellular vesicles. Nat Rev Mol Cell Biol 2022;23(5):369–82. https://doi.org/10.1038/s41580-022-00460-3.

[33]

Azparren-Angulo M, Royo F, Gonzalez E, et al. Extracellular vesicles in hepatology: physiological role, involvement in pathogenesis, and therapeutic opportunities. Pharmacol Ther 2021;218:107683. https://doi.org/10.1016/j.pharmthera.2020.107683.

[34]

Wang X, He Y, Mackowiak B, et al. MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases. Gut 2021;70(4):784–95. https://doi.org/10.1136/gutjnl-2020-322526.

[35]

Rodríguez-Suárez E, Gonzalez E, Hughes C, et al. Quantitative proteomic analysis of hepatocyte-secreted extracellular vesicles reveals candidate markers for liver toxicity. J Proteonomics 2014;103:227–40. https://doi.org/10.1016/j.jprot.2014.04.008.

[36]

Holman NS, Mosedale M, Wolf KK, et al. Subtoxic alterations in hepatocyte-derived exosomes: an early step in drug-induced liver injury? Toxicol Sci 2016;151(2):365–75. https://doi.org/10.1093/toxsci/kfw047.

[37]

Bala S, Petrasek J, Mundkur S, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012;56(5):1946–57. https://doi.org/10.1002/hep.25873.

[38]

Ward J, Kanchagar C, Veksler-Lublinsky I, et al. Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. Proc Natl Acad Sci USA 2014;111(33):12169–74. https://doi.org/10.1073/pnas.1412608111.

[39]

de Jong OG, van Balkom BW, Schiffelers RM, et al. Extracellular vesicles: potential roles in regenerative medicine. Front Immunol 2014;5:608. https://doi.org/10.3389/fimmu.2014.00608.

[40]

Navarro-Alvarez N, Soto-Gutierrez A, Kobayashi N. Stem cell research and therapy for liver disease. Curr Stem Cell Res Ther 2009;4(2):141–6. https://doi.org/10.2174/157488809788167418.

[41]

Fleury A, Martinez MC, Le Lay S. Extracellular vesicles as therapeutic tools in cardiovascular diseases. Front Immunol 2014;5:370. https://doi.org/10.3389/fimmu.2014.00370.

[42]

Chaput N, Théry C. Exosomes: immune properties and potential clinical implementations. Semin Immunopathol 2011;33(5):419–40. https://doi.org/10.1007/s00281-010-0233-9.

[43]

Conde-Vancells J, Rodriguez-Suarez E, Embade N, et al. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 2008;7(12):5157–66. https://doi.org/10.1021/pr8004887.

[44]

Masyuk AI, Huang BQ, Ward CJ, et al. Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia. Am J Physiol Gastrointest Liver Physiol 2010;299(4):G990–9. https://doi.org/10.1152/ajpgi.00093.2010.

[45]

Wang R, Ding Q, Yaqoob U, et al. Exosome adherence and internalization by hepatic stellate cells triggers sphingosine 1-phosphate-dependent migration. J Biol Chem 2015;290(52):30684–96. https://doi.org/10.1074/jbc.M115.671735.

[46]
Szabo G, Saha B, Ambade A. In: Boyer T, Sanyal A, et al., editors. Zakim and Boyer's hepatology. 7th ed. Amsterdam: Elsevier; 2017.
[47]

Robbins PD, Morelli AE. Regulation of immune responses by extracellular vesicles. Nat Rev Immunol 2014;14(3):195–208. https://doi.org/10.1038/nri3622.

[48]

Weil D, di Martino V, Mourey G, et al. Small annexin V-positive platelet-derived microvesicles affect prognosis in cirrhosis: a longitudinal study. Clin Transl Gastroenterol 2021;12(5):e00333. https://doi.org/10.14309/ctg.0000000000000333.

iLIVER
Cite this article:
Badwei N. The potential role of extracellular vesicles as hepatic diagnostic and therapeutic tools: Can the dream come true?. iLIVER, 2024, 3(1). https://doi.org/10.1016/j.iliver.2024.100078

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Received: 30 October 2023
Revised: 24 December 2023
Accepted: 08 January 2024
Published: 06 February 2024
© 2024 The Author(s). Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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