Extracellular Vesicle-mediated Approaches for the Diagnosis and Therapy of MASLD: Current Advances and Future Prospective

Overview

Journal Lipids Health Dis

Publisher Biomed Central

Specialties Biochemistry
Endocrinology

Date 2025 Jan 8

PMID 39773634

Authors

Swasthika Gurjar

Ramanarayana Bhat A

Raghavendra Upadhya

Revathi P Shenoy

Affiliations

Soon will be listed here.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an asymptomatic, multifaceted condition often associated with various risk factors, including fatigue, obesity, insulin resistance, metabolic syndrome, and sleep apnea. The increasing burden of MASLD underscores the critical need for early diagnosis and effective therapies. Owing to the lack of efficient therapies for MASLD, early diagnosis is crucial. Consequently, noninvasive biomarkers and imaging techniques are essential for analyzing disease risk and play a pivotal role in the global diagnostic process. The use of extracellular vesicles has emerged as promising for early diagnosis and therapy of various liver ailments. Herein, a comprehensive summary of the current diagnostic modalities for MASLD is presented, highlighting their advantages and limitations while exploring the potential of extracellular vesicles (EVs) as innovative diagnostic and therapeutic tools for MASLD. With this aim, this review emphasizes an in-depth understanding of the origin of EVs and the pathophysiological alterations of these ectosomes and exosomes in various liver diseases. This review also explores the therapeutic potential of EVs as key components in the future management of liver disease. The dual role of EVs as biomarkers and their therapeutic utility in MASLD essentially highlights their clinical integration to improve MASLD diagnosis and treatment. While EV-based therapies are still in their early stages of development and require substantial research to increase their therapeutic value before they can be used clinically, the diagnostic application of EVs has been extensively explored. Moving forward, developing diagnostic devices leveraging EVs will be crucial in advancing MASLD diagnosis. Thus, the literature summarized provides suitable grounds for clinicians and researchers to explore EVs for devising diagnostic and treatment strategies for MASLD.

References

Lebensztejn D, Wierzbicka A, Socha P, Pronicki M, Skiba E, Werpachowska I . Cytokeratin-18 and hyaluronic acid levels predict liver fibrosis in children with non-alcoholic fatty liver disease. Acta Biochim Pol. 2011; 58(4):563-6. View

Nemeth K, Varga Z, Lenzinger D, Visnovitz T, Koncz A, Hegedus N . Extracellular vesicle release and uptake by the liver under normo- and hyperlipidemia. Cell Mol Life Sci. 2021; 78(23):7589-7604. PMC: 8629784. DOI: 10.1007/s00018-021-03969-6. View

Liu Z, Tian Z, Cao K, Zhang B, Wen Q, Zhou X . TSG101 promotes the proliferation, migration and invasion of hepatocellular carcinoma cells by regulating the PEG10. J Cell Mol Med. 2018; 23(1):70-82. PMC: 6307771. DOI: 10.1111/jcmm.13878. View

Takahashi Y, Dungubat E, Kusano H, Fukusato T . Artificial intelligence and deep learning: New tools for histopathological diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Comput Struct Biotechnol J. 2023; 21:2495-2501. PMC: 10113753. DOI: 10.1016/j.csbj.2023.03.048. View

Hamilton M, Hamilton D, Zderic T . Sedentary behavior as a mediator of type 2 diabetes. Med Sport Sci. 2014; 60:11-26. PMC: 4364419. DOI: 10.1159/000357332. View

Ajmera V, Park C, Caussy C, Singh S, Hernandez C, Bettencourt R . Magnetic Resonance Imaging Proton Density Fat Fraction Associates With Progression of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2018; 155(2):307-310.e2. PMC: 6090543. DOI: 10.1053/j.gastro.2018.04.014. View

Jiao Y, Xu P, Shi H, Chen D, Shi H . Advances on liver cell-derived exosomes in liver diseases. J Cell Mol Med. 2020; 25(1):15-26. PMC: 7810930. DOI: 10.1111/jcmm.16123. View

Mayor S, Pagano R . Pathways of clathrin-independent endocytosis. Nat Rev Mol Cell Biol. 2007; 8(8):603-12. PMC: 7617177. DOI: 10.1038/nrm2216. View

Hirsova P, Ibrahim S, Krishnan A, Verma V, Bronk S, Werneburg N . Lipid-Induced Signaling Causes Release of Inflammatory Extracellular Vesicles From Hepatocytes. Gastroenterology. 2016; 150(4):956-67. PMC: 4808464. DOI: 10.1053/j.gastro.2015.12.037. View

10.

Chen W, Lin F, Feng X, Yao Q, Yu Y, Gao F . MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation. Asian J Pharm Sci. 2024; 19(1):100889. PMC: 10900800. DOI: 10.1016/j.ajps.2024.100889. View

11.

Vallejo M, Nakayasu E, Longo L, Ganiko L, Lopes F, Matsuo A . Lipidomic analysis of extracellular vesicles from the pathogenic phase of Paracoccidioides brasiliensis. PLoS One. 2012; 7(6):e39463. PMC: 3382159. DOI: 10.1371/journal.pone.0039463. View

12.

Liu C, Liu D, Wang S, Gan L, Yang X, Ma C . Identification of the SNARE complex that mediates the fusion of multivesicular bodies with the plasma membrane in exosome secretion. J Extracell Vesicles. 2023; 12(9):e12356. PMC: 10497535. DOI: 10.1002/jev2.12356. View

13.

Li T, Fu Y, Guo Z, Zhu H, Liao H, Niu X . A new cell-free therapeutic strategy for liver regeneration: Human placental mesenchymal stem cell-derived extracellular vesicles. J Tissue Eng. 2022; 13:20417314221132093. PMC: 9597011. DOI: 10.1177/20417314221132093. View

14.

Grigorescu M, Crisan D, Radu C, Grigorescu M, Sparchez Z, Serban A . A novel pathophysiological-based panel of biomarkers for the diagnosis of nonalcoholic steatohepatitis. J Physiol Pharmacol. 2012; 63(4):347-53. View

15.

Gerges S, Wahdan S, Elsherbiny D, El-Demerdash E . Non-alcoholic fatty liver disease: An overview of risk factors, pathophysiological mechanisms, diagnostic procedures, and therapeutic interventions. Life Sci. 2021; 271:119220. DOI: 10.1016/j.lfs.2021.119220. View

16.

Rinella M, Lazarus J, Ratziu V, Francque S, Sanyal A, Kanwal F . A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023; 79(6):1542-1556. DOI: 10.1016/j.jhep.2023.06.003. View

17.

Hydes T, Alam U, Cuthbertson D . The Impact of Macronutrient Intake on Non-alcoholic Fatty Liver Disease (NAFLD): Too Much Fat, Too Much Carbohydrate, or Just Too Many Calories?. Front Nutr. 2021; 8:640557. PMC: 7921724. DOI: 10.3389/fnut.2021.640557. View

18.

Afdhal N . Fibroscan (transient elastography) for the measurement of liver fibrosis. Gastroenterol Hepatol (N Y). 2013; 8(9):605-7. PMC: 3594956. View

19.

Koliaki C, Szendroedi J, Kaul K, Jelenik T, Nowotny P, Jankowiak F . Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab. 2015; 21(5):739-46. DOI: 10.1016/j.cmet.2015.04.004. View

20.

Lone S, Nisar S, Masoodi T, Singh M, Rizwan A, Hashem S . Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments. Mol Cancer. 2022; 21(1):79. PMC: 8932066. DOI: 10.1186/s12943-022-01543-7. View