PDF
Abstract
Exosomes, nanoscale vesicles secreted by diverse cell types, serve as critical mediators of intercellular and interorgan communication in metabolic physiology. Their unique advantages include encapsulating cell-specific biomolecules that reflect cellular origins, enabling noninvasive liquid biopsy for early disease detection through distinct signatures (e.g., miRNA profiles), and functioning as biocompatible drug delivery platforms or bioactive therapeutics in preclinical models. However, despite their transformative potential in metabolic disease diagnostics and therapy, a systematic synthesis of recent advances, molecular mechanisms, and clinical translation challenges is lacking. To address this gap, this review synthesizes cutting-edge insights into exosome biology—spanning composition, biogenesis, secretion, and tissue-specific roles in adipose, liver, muscle, and pancreas—and critically evaluates their dual diagnostic–therapeutic applications across obesity, diabetes, nonalcoholic fatty liver disease (NAFLD), and associated complications. We further delineate key translational hurdles (e.g., production scalability, cargo heterogeneity, and clinical validation) and propose strategies for standardization. By integrating interdisciplinary advances from nanotechnology, omics, and artificial intelligence (AI), this work provides a foundational framework to accelerate the clinical implementation of exosome-based approaches, ultimately advancing precision medicine for metabolic disorders.
Keywords
biomarkers
/
diabetes
/
drug delivery
/
exosomes
/
nonalcoholic fatty liver disease
/
obesity
/
therapy
Cite this article
Download citation ▾
Yanting Wu, Shanshan Yang, You Zhang, Zhiguang Su.
Exosomes in Metabolic Diseases: From Molecular Mechanisms to Clinical Applications.
MEDCOMM - Future Medicine, 2025, 4(3): e70031 DOI:10.1002/mef2.70031
| [1] |
X. D. Zhou, Q. F. Chen, G. Targher, et al., “Global Burden of Disease Attributable to Metabolic Risk Factors in Adolescents and Young Adults Aged 15–39, 1990–2021,” Clinical Nutrition 43, no. 12 (2024): 391–404.
|
| [2] |
N. W. S. Chew, C. H. Ng, D. J. H. Tan, et al., “The Global Burden of Metabolic Disease: Data From 2000 to 2019,” Cell Metabolism 35, no. 3 (2023): 414–428.e3.
|
| [3] |
B. T. Pan and R. M. Johnstone, “Fate of the Transferrin Receptor During Maturation of Sheep Reticulocytes In Vitro—Selective Externalization of the Receptor,” Cell 33, no. 3 (1983): 967–978.
|
| [4] |
K. Cunha e Rocha, W. Ying, and J. M. Olefsky, “Exosome-Mediated Impact on Systemic Metabolism,” Annual Review of Physiology 86 (2024): 225–253.
|
| [5] |
J. Zuo, H. Yan, S. Qin, et al., “Extracellular Vesicles in Cancer Drug Resistance: Mechanistic Insights and Therapeutic Implications,” MedComm-Oncology 3, no. 4 (2024): e94.
|
| [6] |
T. V. Rohm, K. Cunha e Rocha, and J. M. Olefsky, “Metabolic Messengers: Small Extracellular Vesicles,” Nature Metabolism 7, no. 2 (2025): 253–262.
|
| [7] |
Z. Deng, A. Poliakov, R. W. Hardy, et al., “Adipose Tissue Exosome-Like Vesicles Mediate Activation of Macrophage-Induced Insulin Resistance,” Diabetes 58, no. 11 (2009): 2498–2505.
|
| [8] |
A. P. Lewis and C. L. Jopling, “Regulation and Biological Function of the Liver-Specific miR-122,” Biochemical Society Transactions 38, no. 6 (2010): 1553–1557.
|
| [9] |
S. D. Jordan, M. Krüger, D. M. Willmes, et al., “Obesity-Induced Overexpression of miRNA-143 Inhibits Insulin-Stimulated AKT Activation and Impairs Glucose Metabolism,” Nature Cell Biology 13, no. 4 (2011): 434–446.
|
| [10] |
E. S. Koeck, T. Iordanskaia, S. Sevilla, et al., “Adipocyte Exosomes Induce Transforming Growth Factor Beta Pathway Dysregulation in Hepatocytes: A Novel Paradigm for Obesity-Related Liver Disease,” Journal of Surgical Research 192, no. 2 (2014): 268–275.
|
| [11] |
M. J. Lee, D. H. Park, and J. H. Kang, “Exosomes as the Source of Biomarkers of Metabolic Diseases,” Annals of Pediatric Endocrinology & Metabolism 21, no. 3 (2016): 119–125.
|
| [12] |
W. Ying, M. Riopel, G. Bandyopadhyay, et al., “Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity,” Cell 171, no. 2 (2017): 372–384.e12.
|
| [13] |
Y. Sun, Q. Tao, X. Wu, L. Zhang, Q. Liu, and L. Wang, “The Utility of Exosomes in Diagnosis and Therapy of Diabetes Mellitus and Associated Complications,” Frontiers in Endocrinology 12 (2021): 756581.
|
| [14] |
N. Wang, J. Li, Z. Hu, E. E. Ngowi, B. Yan, and A. Qiao, “Exosomes: New Insights Into the Pathogenesis of Metabolic Syndrome,” Biology 12, no. 12 (2023): 1480.
|
| [15] |
Z. Yang, T. Tian, J. Kong, and H. Chen, “ChatExosome: An Artificial Intelligence (AI) Agent Based on Deep Learning of Exosomes Spectroscopy for Hepatocellular Carcinoma (HCC) Diagnosis,” Analytical Chemistry 97, no. 8 (2025): 4643–4652.
|
| [16] |
R. Li, H. Wang, X. Wang, et al., “MSC-EVs and UCB-EVs Promote Skin Wound Healing and Spatial Transcriptome Analysis,” Scientific Reports 15, no. 1 (2025): 4006.
|
| [17] |
T. Li, Y. Yang, H. Qi, et al., “CRISPR/Cas9 Therapeutics: Progress and Prospects,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 36.
|
| [18] |
Y. Guo, Z. Wan, P. Zhao, et al., “Ultrasound Triggered Topical Delivery of Bmp7 mRNA for White Fat Browning Induction via Engineered Smart Exosomes,” Journal of Nanobiotechnology 19, no. 1 (2021): 402.
|
| [19] |
D. K. Jeppesen, Q. Zhang, J. L. Franklin, and R. J. Coffey, “Extracellular Vesicles and Nanoparticles: Emerging Complexities,” Trends in Cell Biology 33, no. 8 (2023): 667–681.
|
| [20] |
D. Zabeo, A. Cvjetkovic, C. Lässer, M. Schorb, J. Lötvall, and J. L. Höög, “Exosomes Purified From a Single Cell Type Have Diverse Morphology,” Journal of Extracellular Vesicles 6, no. 1 (2017): 1329476.
|
| [21] |
N. Dilsiz, “A Comprehensive Review on Recent Advances in Exosome Isolation and Characterization: Toward Clinical Applications,” Translational Oncology 50 (2024): 102121.
|
| [22] |
S. Gurung, D. Perocheau, L. Touramanidou, and J. Baruteau, “The Exosome Journey: From Biogenesis to Uptake and Intracellular Signalling,” Cell Communication and Signaling 19, no. 1 (2021): 47.
|
| [23] |
M. F. Baietti, Z. Zhang, E. Mortier, et al., “Syndecan-Syntenin-ALIX Regulates the Biogenesis of Exosomes,” Nature Cell Biology 14, no. 7 (2012): 677–685.
|
| [24] |
R. Kalluri and V. S. LeBleu, “The Biology, Function, and Biomedical Applications of Exosomes,” Science 367, no. 6478 (2020): eaau6977.
|
| [25] |
W. M. Henne, N. J. Buchkovich, and S. D. Emr, “The ESCRT Pathway,” Developmental Cell 21, no. 1 (2011): 77–91.
|
| [26] |
D. Ha, N. Yang, and V. Nadithe, “Exosomes as Therapeutic Drug Carriers and Delivery Vehicles Across Biological Membranes: Current Perspectives and Future Challenges,” Acta Pharmaceutica Sinica B 6, no. 4 (2016): 287–296.
|
| [27] |
J. Kowal, G. Arras, M. Colombo, et al., “Proteomic Comparison Defines Novel Markers to Characterize Heterogeneous Populations of Extracellular Vesicle Subtypes,” Proceedings of the National Academy of Sciences 113, no. 8 (2016): E968–E977.
|
| [28] |
Z. Andreu and M. Yáñez-Mó, “Tetraspanins in Extracellular Vesicle Formation and Function,” Frontiers in Immunology 5 (2014): 442.
|
| [29] |
P. D. Robbins and A. E. Morelli, “Regulation of Immune Responses by Extracellular Vesicles,” Nature Reviews Immunology 14, no. 3 (2014): 195–208.
|
| [30] |
A. Hoshino, B. Costa-Silva, T. L. Shen, et al., “Tumour Exosome Integrins Determine Organotropic Metastasis,” Nature 527, no. 7578 (2015): 329–335.
|
| [31] |
H. Zhang, T. Deng, R. Liu, et al., “Exosome-Delivered EGFR Regulates Liver Microenvironment to Promote Gastric Cancer Liver Metastasis,” Nature Communications 8 (2017): 15016.
|
| [32] |
K. Al-Nedawi, B. Meehan, J. Micallef, et al., “Intercellular Transfer of the Oncogenic Receptor EGFRvIII by Microvesicles Derived From Tumour Cells,” Nature Cell Biology 10, no. 5 (2008): 619–624.
|
| [33] |
M. Shimoda and R. Khokha, “Metalloproteinases in Extracellular Vesicles,” Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1864, no. 11 Pt A (2017): 1989–2000.
|
| [34] |
K. Trajkovic, C. Hsu, S. Chiantia, et al., “Ceramide Triggers Budding of Exosome Vesicles Into Multivesicular Endosomes,” Science 319, no. 5867 (2008): 1244–1247.
|
| [35] |
Y. Zhou, H. Ren, B. Dai, et al., “Hepatocellular Carcinoma-Derived Exosomal miRNA-21 Contributes to Tumor Progression by Converting Hepatocyte Stellate Cells to Cancer-Associated Fibroblasts,” Journal of Experimental & Clinical Cancer Research 37, no. 1 (2018): 324.
|
| [36] |
A. Montecalvo, A. T. Larregina, W. J. Shufesky, et al., “Mechanism of Transfer of Functional MicroRNAs Between Mouse Dendritic Cells via Exosomes,” Blood 119, no. 3 (2012): 756–766.
|
| [37] |
J. J. Liu and H. W. Wang, “Cryo-Electron Microscopy of Endogenous Yeast Exosomes,” Methods in Molecular Biology 2062 (2020): 401–415.
|
| [38] |
C. Lässer, V. Seyed Alikhani, K. Ekström, et al., “Human Saliva, Plasma and Breast Milk Exosomes Contain RNA: Uptake by Macrophages,” Journal of Translational Medicine 9 (2011): 9.
|
| [39] |
F. Zhang, J. Jiang, H. Qian, Y. Yan, and W. Xu, “Exosomal circRNA: Emerging Insights Into Cancer Progression and Clinical Application Potential,” Journal of Hematology & Oncology 16, no. 1 (2023): 67.
|
| [40] |
Y. Li, Q. Zheng, C. Bao, et al., “Circular RNA Is Enriched and Stable in Exosomes: A Promising Biomarker for Cancer Diagnosis,” Cell Research 25, no. 8 (2015): 981–984.
|
| [41] |
J. Gao, P. Chen, Z. Li, et al., “Identification of lncRNA in Circulating Exosomes as Potential Biomarkers for MCI Among the Elderly,” Journal of Affective Disorders 370 (2025): 401–411.
|
| [42] |
A. Narayanan, S. Iordanskiy, R. Das, et al., “Exosomes Derived From HIV-1-infected Cells Contain Trans-Activation Response Element Rna,” Journal of Biological Chemistry 288, no. 27 (2013): 20014–20033.
|
| [43] |
E. Barberis, V. V. Vanella, M. Falasca, et al., “Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection,” Frontiers in Molecular Biosciences 8 (2021): 632290.
|
| [44] |
D. M. Pegtel, K. Cosmopoulos, D. A. Thorley-Lawson, et al., “Functional Delivery of Viral miRNAs via Exosomes,” Proceedings of the National Academy of Sciences 107, no. 14 (2010): 6328–6333.
|
| [45] |
C. R. Alarcón, H. Lee, H. Goodarzi, N. Halberg, and S. F. Tavazoie, “N6-Methyladenosine Marks Primary MicroRNAs for Processing,” Nature 519, no. 7544 (2015): 482–485.
|
| [46] |
D. Fitzner, M. Schnaars, D. van Rossum, et al., “Selective Transfer of Exosomes From Oligodendrocytes to Microglia by Macropinocytosis,” Journal of Cell Science 124, no. pt. 3 (2011): 447–458.
|
| [47] |
T. Becker, S. E. Horvath, L. Böttinger, N. Gebert, G. Daum, and N. Pfanner, “Role of Phosphatidylethanolamine in the Biogenesis of Mitochondrial Outer Membrane Proteins,” Journal of Biological Chemistry 288, no. 23 (2013): 16451–16459.
|
| [48] |
J. Skog, T. Würdinger, S. van Rijn, et al., “Glioblastoma Microvesicles Transport RNA and Proteins That Promote Tumour Growth and Provide Diagnostic Biomarkers,” Nature Cell Biology 10, no. 12 (2008): 1470–1476.
|
| [49] |
R. Tenchov, J. M. Sasso, X. Wang, W. S. Liaw, C. A. Chen, and Q. A. Zhou, “Exosomes—Nature's Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics,” ACS Nano 16, no. 11 (2022): 17802–17846.
|
| [50] |
A. Magdy Beshbishy, S. Alghamdi, T. E. Onyiche, et al., “Biogenesis, Biologic Function and Clinical Potential of Exosomes in Different Diseases,” Applied Sciences 10, no. 13 (2020): 4428.
|
| [51] |
B. K. Thakur, H. Zhang, A. Becker, et al., “Double-Stranded DNA in Exosomes: A Novel Biomarker in Cancer Detection,” Cell Research 24, no. 6 (2014): 766–769.
|
| [52] |
D. K. Jeppesen, A. M. Fenix, J. L. Franklin, et al., “Reassessment of Exosome Composition,” Cell 177, no. 2 (2019): 428–445.e18.
|
| [53] |
N. P. Hessvik and A. Llorente, “Current Knowledge on Exosome Biogenesis and Release,” Cellular and Molecular Life Sciences 75, no. 2 (2018): 193–208.
|
| [54] |
R. Palmulli, M. Couty, M. C. Piontek, et al., “CD63 Sorts Cholesterol Into Endosomes for Storage and Distribution via Exosomes,” Nature Cell Biology 26, no. 7 (2024): 1093–1109.
|
| [55] |
L. Qian, X. Yang, S. Li, et al., “Reduced O-GlcNAcylation of SNAP-23 Promotes Cisplatin Resistance by Inducing Exosome Secretion in Ovarian Cancer,” Cell Death Discovery 7, no. 1 (2021): 112.
|
| [56] |
Y. Wei, D. Wang, F. Jin, et al., “Pyruvate Kinase Type M2 Promotes Tumour Cell Exosome Release via Phosphorylating Synaptosome-Associated Protein 23,” Nature Communications 8 (2017): 14041.
|
| [57] |
M. Ruiz-Martinez, A. Navarro, R. M. Marrades, et al., “YKT6 Expression, Exosome Release, and Survival in Non-Small Cell Lung Cancer,” Oncotarget 7, no. 32 (2016): 51515–51524.
|
| [58] |
L. Yang, X. Peng, Y. Li, et al., “Long Non-Coding RNA HOTAIR Promotes Exosome Secretion by Regulating RAB35 and SNAP23 in Hepatocellular Carcinoma,” Molecular Cancer 18 (2019): 78.
|
| [59] |
S. Koike and R. Jahn, “Rab GTPases and Phosphoinositides Fine-Tune SNAREs Dependent Targeting Specificity of Intracellular Vesicle Traffic,” Nature Communications 15, no. 1 (2024): 2508.
|
| [60] |
M. Ostrowski, N. B. Carmo, S. Krumeich, et al., “Rab27a and Rab27b Control Different Steps of the Exosome Secretion Pathway,” Nature Cell Biology 12, no. 1 (2010): 19–30.
|
| [61] |
S. B. Arya, S. P. Collie, and C. A. Parent, “The Ins-and-Outs of Exosome Biogenesis, Secretion, and Internalization,” Trends in Cell Biology 34, no. 2 (2024): 90–108.
|
| [62] |
I. Parolini, C. Federici, C. Raggi, et al., “Microenvironmental pH Is a Key Factor for Exosome Traffic in Tumor Cells,” Journal of Biological Chemistry 284, no. 49 (2009): 34211–34222.
|
| [63] |
C. Wang, J. Tu, S. Zhang, et al., “Different Regions of Synaptic Vesicle Membrane Regulate VAMP2 Conformation for the SNARE Assembly,” Nature Communications 11, no. 1 (2020): 1531.
|
| [64] |
Y. T. Sato, K. Umezaki, S. Sawada, et al., “Engineering Hybrid Exosomes by Membrane Fusion With Liposomes,” Scientific Reports 6 (2016): 21933.
|
| [65] |
E. Bonsergent, E. Grisard, J. Buchrieser, O. Schwartz, C. Théry, and G. Lavieu, “Quantitative Characterization of Extracellular Vesicle Uptake and Content Delivery Within Mammalian Cells,” Nature Communications 12, no. 1 (2021): 1864.
|
| [66] |
G. Morad, C. V. Carman, E. J. Hagedorn, et al., “Tumor-Derived Extracellular Vesicles Breach the Intact Blood–Brain Barrier via Transcytosis,” ACS Nano 13, no. 12 (2019): 13853–13865.
|
| [67] |
B. S. Joshi and I. S. Zuhorn, “Heparan Sulfate Proteoglycan-Mediated Dynamin-Dependent Transport of Neural Stem Cell Exosomes in an In Vitro Blood–Brain Barrier Model,” European Journal of Neuroscience 53, no. 3 (2021): 706–719.
|
| [68] |
W. A. Banks, P. Sharma, K. M. Bullock, K. M. Hansen, N. Ludwig, and T. L. Whiteside, “Transport of Extracellular Vesicles Across the Blood–Brain Barrier: Brain Pharmacokinetics and Effects of Inflammation,” International Journal of Molecular Sciences 21, no. 12 (2020): 4407.
|
| [69] |
S. Guan, Q. Li, P. Liu, X. Xuan, and Y. Du, “Experimental Immunology Umbilical Cord Blood-Derived Dendritic Cells Loaded With BGC823 Tumor Antigens and DC-Derived Exosomes Stimulate Efficient Cytotoxic T-Lymphocyte Responses and Antitumor Immunity In Vitro and In Vivo,” Central European Journal of Immunology 2 (2014): 142–151.
|
| [70] |
S. Munich, A. Sobo-Vujanovic, W. J. Buchser, D. Beer-Stolz, and N. L. Vujanovic, “Dendritic Cell Exosomes Directly Kill Tumor Cells and Activate Natural Killer Cells via TNF Superfamily Ligands,” Oncoimmunology 1, no. 7 (2012): 1074–1083.
|
| [71] |
R. He and Y. Chen, “The Role of Adipose Tissue-Derived Exosomes in Chronic Metabolic Disorders,” Current Medical Science 44, no. 3 (2024): 463–474.
|
| [72] |
Y. Pan, X. Hui, R. L. C. Hoo, et al., “Adipocyte-Secreted Exosomal MicroRNA-34a Inhibits M2 Macrophage Polarization to Promote Obesity-Induced Adipose Inflammation,” Journal of Clinical Investigation 129, no. 2 (2019): 834–849.
|
| [73] |
S. E. Flaherty, A. Grijalva, X. Xu, E. Ables, A. Nomani, and A. W. Ferrante, “A Lipase-Independent Pathway of Lipid Release and Immune Modulation by Adipocytes,” Science 363, no. 6430 (2019): 989–993.
|
| [74] |
Y. Chen, F. Siegel, S. Kipschull, et al., “miR-155 Regulates Differentiation of Brown and Beige Adipocytes via a Bistable Circuit,” Nature Communications 4 (2013): 1769.
|
| [75] |
J. B. Tryggestad, A. M. Teague, D. P. Sparling, S. Jiang, and S. D. Chernausek, “Macrophage-Derived MicroRNA-155 Increases in Obesity and Influences Adipocyte Metabolism by Targeting Peroxisome Proliferator-Activated Receptor Gamma,” Obesity 27, no. 11 (2019): 1856–1864.
|
| [76] |
W. Ying, H. Gao, F. C. G. Dos Reis, et al., “MiR-690, an Exosomal-Derived miRNA From M2-polarized Macrophages, Improves Insulin Sensitivity in Obese Mice,” Cell Metabolism 33, no. 4 (2021): 781–790.e5.
|
| [77] |
A. Mikłosz and A. Chabowski, “Adipose-Derived Mesenchymal Stem Cells Therapy as a New Treatment Option for Diabetes Mellitus,” Journal of Clinical Endocrinology & Metabolism 108, no. 8 (2023): 1889–1897.
|
| [78] |
C. J. Li, Q. H. Fang, M. L. Liu, and J. N. Lin, “Current Understanding of the Role of Adipose-Derived Extracellular Vesicles in Metabolic Homeostasis and Diseases: Communication From the Distance Between Cells/Tissues,” Theranostics 10, no. 16 (2020): 7422–7435.
|
| [79] |
E. Cione, R. Cannataro, L. Gallelli, G. De Sarro, and M. C. Caroleo, “Exosome MicroRNAs in Metabolic Syndrome as Tools for the Early Monitoring of Diabetes and Possible Therapeutic Options,” Pharmaceuticals 14, no. 12 (2021): 1257.
|
| [80] |
S. Kersting and H. Mziaut, “Mir-132 Controls Pancreatic Beta-Cell Proliferation and Survival Through the Pten/Akt/Foxo3 Signaling,” Molecular Metabolism 31 (2020): 150–162.
|
| [81] |
R. Dusaulcy, S. Handgraaf, F. Visentin, C. Vesin, J. Philippe, and Y. Gosmain, “miR-132-3p Is a Positive Regulator of Alpha-Cell Mass and Is Downregulated in Obese Hyperglycemic Mice,” Molecular Metabolism 22 (2019): 84–95.
|
| [82] |
X. Cui, L. You, L. Zhu, et al., “Change in Circulating Microrna Profile of Obese Children Indicates Future Risk of Adult Diabetes,” Metabolism: Clinical and Experimental 78 (2018): 95–105.
|
| [83] |
B. Qian, Y. Yang, N. Tang, et al., “M1 Macrophage-Derived Exosomes Impair Beta Cell Insulin Secretion via miR-212-5p by Targeting SIRT2 and Inhibiting Akt/GSK-3β/β-Catenin Pathway in Mice,” Diabetologia 64, no. 9 (2021): 2037–2051.
|
| [84] |
T. Thomou, M. A. Mori, J. M. Dreyfuss, et al., “Adipose-Derived Circulating miRNAs Regulate Gene Expression in Other Tissues,” Nature 542, no. 7642 (2017): 450–455.
|
| [85] |
H. C. Song, D. M. Li, L. H. Shuo, et al., “Gonadal White Adipose Tissue-Derived Exosomal MiR-222 Promotes Obesity-Associated Insulin Resistance,” Aging-US 12, no. 22 (2020): 22719–22743.
|
| [86] |
B. Yue, H. Wang, X. Cai, et al., “Adipose-Secreted Exosomes and Their Pathophysiologic Effects on Skeletal Muscle,” International Journal of Molecular Sciences 23, no. 20 (2022): 12411.
|
| [87] |
L. Guo, M. Quan, W. Pang, Y. Yin, and F. Li, “Cytokines and Exosomal miRNAs in Skeletal Muscle-Adipose Crosstalk,” Trends in Endocrinology & Metabolism 34, no. 10 (2023): 666–681.
|
| [88] |
Y. Yu, H. Du, S. Wei, et al., “Adipocyte-Derived Exosomal MiR-27a Induces Insulin Resistance in Skeletal Muscle Through Repression of PPARγ,” Theranostics 8, no. 8 (2018): 2171–2188.
|
| [89] |
Y. Tang, L. J. Yang, H. Liu, et al., “Exosomal miR-27b-3p Secreted by Visceral Adipocytes Contributes to Endothelial Inflammation and Atherogenesis,” Cell Reports 42, no. 1 (2023): 111948.
|
| [90] |
X. Zhang, S. Yang, J. Chen, and Z. Su, “Unraveling the Regulation of Hepatic Gluconeogenesis,” Frontiers in Endocrinology 9 (2019): 802.
|
| [91] |
Y. Jiao, P. Xu, H. Shi, D. Chen, and H. Shi, “Advances on Liver Cell-Derived Exosomes in Liver Diseases,” Journal of Cellular and Molecular Medicine 25, no. 1 (2021): 15–26.
|
| [92] |
H. Nojima, C. M. Freeman, R. M. Schuster, et al., “Hepatocyte Exosomes Mediate Liver Repair and Regeneration via Sphingosine-1-Phosphate,” Journal of Hepatology 64, no. 1 (2016): 60–68.
|
| [93] |
Y. Zhao, M. F. Zhao, S. Jiang, et al., “Liver Governs Adipose Remodelling via Extracellular Vesicles in Response to Lipid Overload,” Nature Communications 11, no. 1 (2020): 719.
|
| [94] |
M. Babuta, I. Furi, S. Bala, et al., “Dysregulated Autophagy and Lysosome Function Are Linked to Exosome Production by Micro-RNA 155 in Alcoholic Liver Disease,” Hepatology 70, no. 6 (2019): 2123–2141.
|
| [95] |
Y. Ji, Z. Luo, H. Gao, et al., “Hepatocyte-Derived Exosomes From Early Onset Obese Mice Promote Insulin Sensitivity Through miR-3075,” Nature Metabolism 3, no. 9 (2021): 1163–1174.
|
| [96] |
L. Wan, T. Xia, Y. Du, et al., “Exosomes From Activated Hepatic Stellate Cells Contain GLUT1 and PKM2: A Role for Exosomes in Metabolic Switch of Liver Nonparenchymal Cells,” FASEB Journal 33, no. 7 (2019): 8530–8542.
|
| [97] |
J. Jia, L. Wang, Y. Zhou, P. Zhang, and X. Chen, “Muscle-Derived Extracellular Vesicles Mediate Crosstalk Between Skeletal Muscle and Other Organs,” Frontiers in Physiology 15 (2025): 1501957.
|
| [98] |
S. Zanotti, S. Gibertini, F. Blasevich, et al., “Exosomes and Exosomal miRNAs From Muscle-Derived Fibroblasts Promote Skeletal Muscle Fibrosis,” Matrix Biology 74 (2018): 77–100.
|
| [99] |
A. Jalabert, L. Reininger, E. Berger, et al., “Profiling of ob/ob Mice Skeletal Muscle Exosome-Like Vesicles Demonstrates Combined Action of miRNAs, Proteins and Lipids to Modulate Lipid Homeostasis in Recipient Cells,” Scientific Reports 11, no. 1 (2021): 21626.
|
| [100] |
A. Jalabert, G. Vial, C. Guay, et al., “Exosome-Like Vesicles Released From Lipid-Induced Insulin-Resistant Muscles Modulate Gene Expression and Proliferation of Beta Recipient Cells in Mice,” Diabetologia 59, no. 5 (2016): 1049–1058.
|
| [101] |
C. Castaño, M. Mirasierra, M. Vallejo, A. Novials, and M. Párrizas, “Delivery of Muscle-Derived Exosomal miRNAs Induced by HIIT Improves Insulin Sensitivity Through Down-Regulation of Hepatic FoxO1 in Mice,” Proceedings of the National Academy of Sciences 117, no. 48 (2020): 30335–30343.
|
| [102] |
J. P. Barlow and T. P. Solomon, “Do Skeletal Muscle-Secreted Factors Influence the Function of Pancreatic β-Cells?,” American Journal of Physiology-Endocrinology and Metabolism 314, no. 4 (2018): E297–E307.
|
| [103] |
D. Cui, X. Feng, S. Lei, et al., “Pancreatic β-Cell Failure, Clinical Implications, and Therapeutic Strategies in Type 2 Diabetes,” Chinese Medical Journal 137, no. 7 (2024): 791–805.
|
| [104] |
Y. Liu, S. He, R. Zhou, et al., “Nuclear Factor-Y in Mouse Pancreatic β-Cells Plays a Crucial Role in Glucose Homeostasis by Regulating β-Cell Mass and Insulin Secretion,” Diabetes 70, no. 8 (2021): 1703–1716.
|
| [105] |
H. S. Lee, J. Jeong, and K. J. Lee, “Characterization of Vesicles Secreted From Insulinoma NIT-1 Cells,” Journal of Proteome Research 8, no. 6 (2009): 2851–2862.
|
| [106] |
Q. Guo, Y. Lu, Y. Huang, et al., “Exosomes From β-Cells Promote Differentiation of Induced Pluripotent Stem Cells Into Insulin-Producing Cells Through MicroRNA-Dependent Mechanisms,” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 14 (2021): 4767–4782.
|
| [107] |
Q. Zhu, J. Kang, H. Miao, et al., “Low-Dose Cytokine-Induced Neutral Ceramidase Secretion From INS-1 Cells via Exosomes and Its Anti-Apoptotic Effect,” FEBS journal 281, no. 12 (2014): 2861–2870.
|
| [108] |
C. Cianciaruso, E. A. Phelps, M. Pasquier, et al., “Primary Human and Rat β-Cells Release the Intracellular Autoantigens GAD65, IA-2, and Proinsulin in Exosomes Together With Cytokine-Induced Enhancers of Immunity,” Diabetes 66, no. 2 (2017): 460–473.
|
| [109] |
C. Guay and R. Regazzi, “Exosomes as New Players in Metabolic Organ Cross-Talk,” Diabetes, Obesity and Metabolism 19 (2017): 137–146.
|
| [110] |
H. Xu, X. Du, J. Xu, et al., “Pancreatic β Cell MicroRNA-26a Alleviates Type 2 Diabetes by Improving Peripheral Insulin Sensitivity and Preserving β Cell Function,” PLoS Biology 18, no. 2 (2020): e3000603.
|
| [111] |
N. Brusco, G. Sebastiani, G. Di Giuseppe, et al., “Intra-Islet Insulin Synthesis Defects Are Associated With Endoplasmic Reticulum Stress and Loss of Beta Cell Identity in Human Diabetes,” Diabetologia 66, no. 2 (2023): 354–366.
|
| [112] |
X. Fang, Y. Zhang, Y. Zhang, et al., “Endothelial Extracellular Vesicles: Their Possible Function and Clinical Significance in Diabetic Vascular Complications,” Journal of Translational Medicine 22, no. 1 (2024): 944.
|
| [113] |
V. Cantaluppi, L. Biancone, F. Figliolini, et al., “Microvesicles Derived From Endothelial Progenitor Cells Enhance Neoangiogenesis of Human Pancreatic Islets,” Cell Transplantation 21, no. 6 (2012): 1305–1320.
|
| [114] |
L. Zhu, H. T. Sun, S. Wang, et al., “Isolation and Characterization of Exosomes for Cancer Research,” Journal of Hematology & Oncology 13, no. 1 (2020): 152.
|
| [115] |
K. S. Visan, R. J. Lobb, S. Ham, et al., “Comparative Analysis of Tangential Flow Filtration and Ultracentrifugation, Both Combined With Subsequent Size Exclusion Chromatography, for the Isolation of Small Extracellular Vesicles,” Journal of Extracellular Vesicles 11, no. 9 (2022): e12266.
|
| [116] |
A. K. Ludwig, K. De Miroschedji, T. R. Doeppner, et al., “Precipitation With Polyethylene Glycol Followed by Washing and Pelleting by Ultracentrifugation Enriches Extracellular Vesicles From Tissue Culture Supernatants in Small and Large Scales,” Journal of Extracellular Vesicles 7, no. 1 (2018): 1528109.
|
| [117] |
A. Hoshino, H. S. Kim, L. Bojmar, et al., “Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers,” Cell 182, no. 4 (2020): 1044–1061.e18.
|
| [118] |
H. Sun, P. Saeedi, S. Karuranga, et al., “IDF Diabetes Atlas: Global, Regional and Country-Level Diabetes Prevalence Estimates for 2021 and Projections for 2045 (Vol 183, 109119, 2022),” Diabetes Research and Clinical Practice 204 (2023): 109119.
|
| [119] |
S. A. Hinger, D. J. Cha, J. L. Franklin, et al., “Diverse Long RNAs Are Differentially Sorted Into Extracellular Vesicles Secreted by Colorectal Cancer Cells,” Cell Reports 25, no. 3 (2018): 715–725.e4.
|
| [120] |
A. J. Lakhter, R. E. Pratt, R. E. Moore, et al., “Beta Cell Extracellular Vesicle miR-21-5p Cargo Is Increased in Response to Inflammatory Cytokines and Serves as a Biomarker of Type 1 Diabetes,” Diabetologia 61, no. 5 (2018): 1124–1134.
|
| [121] |
T. Tesovnik, J. Kovač, K. Pohar, et al., “Extracellular Vesicles Derived Human-miRNAs Modulate the Immune System in Type 1 Diabetes,” Frontiers in Cell and Developmental Biology 8 (2020): 202.
|
| [122] |
H. Pang, W. Fan, X. Shi, et al., “Characterization of lncRNA Profiles of Plasma-Derived Exosomes From Type 1 Diabetes Mellitus,” Frontiers in Endocrinology 13 (2022): 822221.
|
| [123] |
M. Katayama, O. P. B. Wiklander, T. Fritz, et al., “Circulating Exosomal miR-20b-5p Is Elevated in Type 2 Diabetes and Could Impair Insulin Action in Human Skeletal Muscle,” Diabetes 68, no. 3 (2019): 515–526.
|
| [124] |
X. Chen, F. Tian, Z. Sun, G. Zeng, and P. Tang, “Elevation of Circulating miR-210 Participates in the Occurrence and Development of Type 2 Diabetes Mellitus and Its Complications,” Journal of Diabetes Research 2022 (2022): 1–10.
|
| [125] |
I. Sidorkiewicz, M. Niemira, K. Maliszewska, et al., “Circulating miRNAs as a Predictive Biomarker of the Progression From Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study,” Journal of Clinical Medicine 9, no. 7 (2020): 2184.
|
| [126] |
Y. U. Bae, Y. Kim, H. Lee, et al., “Bariatric Surgery Alters MicroRNA Content of Circulating Exosomes in Patients With Obesity,” Obesity 27, no. 2 (2019): 264–271.
|
| [127] |
G. Catanzaro, F. Conte, S. Trocchianesi, et al., “Network Analysis Identifies Circulating miR-155 as Predictive Biomarker of Type 2 Diabetes Mellitus Development in Obese Patients: A Pilot Study,” Scientific Reports 13, no. 1 (2023): 19496.
|
| [128] |
A. Jones, K. M. Danielson, M. C. Benton, et al., “miRNA Signatures of Insulin Resistance in Obesity,” Obesity 25, no. 10 (2017): 1734–1744.
|
| [129] |
L. Xiong, L. Chen, L. Wu, et al., “Lipotoxicity-Induced circGlis3 Impairs Beta Cell Function and Is Transmitted by Exosomes to Promote Islet Endothelial Cell Dysfunction,” Diabetologia 65, no. 1 (2022): 188–205.
|
| [130] |
W. Fan, H. Pang, X. Li, Z. Xie, G. Huang, and Z. Zhou, “Plasma-Derived Exosomal miRNAs as Potentially Novel Biomarkers for Latent Autoimmune Diabetes in Adults,” Diabetes Research and Clinical Practice 197 (2023): 110570.
|
| [131] |
J. Wang, Y. Tao, F. Zhao, T. Liu, X. Shen, and L. Zhou, “Expression of Urinary Exosomal miRNA-615-3p and miRNA-3147 in Diabetic Kidney Disease and Their Association With Inflammation and Fibrosis,” Renal Failure 45, no. 1 (2023): 2121929.
|
| [132] |
W. Li, S. Yang, R. Qiao, and J. Zhang, “Potential Value of Urinary Exosome-Derived let-7c-5p in the Diagnosis and Progression of Type II Diabetic Nephropathy,” Clinical Laboratory 64, no. 5 (2018): 709–718.
|
| [133] |
Y. Pan, H. Yang, T. Chen, et al., “Extracellular Vesicles Metabolic Changes Reveals Plasma Signature in Stage-Dependent Diabetic Kidney Disease,” Renal Failure 44, no. 1 (2022): 1850–1859.
|
| [134] |
D. Deng, S. Yang, X. Yu, et al., “Aging-Induced Short-Chain Acyl-CoA Dehydrogenase Promotes Age-Related Hepatic Steatosis by Suppressing Lipophagy,” Aging Cell 23, no. 10 (2024): e14256.
|
| [135] |
X. Yu, X. Bian, H. Zhang, S. Yang, D. Cui, and Z. Su, “Liraglutide Ameliorates Hepatic Steatosis via Retinoic Acid Receptor-Related Orphan Receptor α-Mediated Autophagy Pathway,” IUBMB Life 75, no. 10 (2023): 856–867.
|
| [136] |
D. Dasgupta, Y. Nakao, A. S. Mauer, et al., “IRE1A Stimulates Hepatocyte-Derived Extracellular Vesicles That Promote Inflammation in Mice With Steatohepatitis,” Gastroenterology 159, no. 4 (2020): 1487–1503.e17.
|
| [137] |
P. Hirsova, S. H. Ibrahim, V. K. Verma, et al., “Extracellular Vesicles in Liver Pathobiology: Small Particles With Big Impact,” Hepatology 64, no. 6 (2016): 2219–2233.
|
| [138] |
Y. Lee and J. H. Kim, “The Emerging Roles of Extracellular Vesicles as Intercellular Messengers in Liver Physiology and Pathology,” Clinical and Molecular Hepatology 28, no. 4 (2022): 706–724.
|
| [139] |
D. Povero, A. Eguchi, H. Li, et al., “Circulating Extracellular Vesicles With Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease,” PLoS One 9, no. 12 (2014): e113651.
|
| [140] |
L. A. Newman, Z. Useckaite, J. Johnson, M. J. Sorich, A. M. Hopkins, and A. Rowland, “Selective Isolation of Liver-Derived Extracellular Vesicles Redefines Performance of miRNA Biomarkers for Non-Alcoholic Fatty Liver Disease,” Biomedicines 10, no. 1 (2022): 195.
|
| [141] |
A. Tamimi, M. Javid, N. Sedighi-Pirsaraei, and A. Mirdamadi, “Exosome Prospects in the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease,” Frontiers in Medicine 11 (2024): 1420281.
|
| [142] |
V. P. Tryndyak, J. R. Latendresse, B. Montgomery, et al., “Plasma MicroRNAs Are Sensitive Indicators of Inter-Strain Differences in the Severity of Liver Injury Induced in Mice by a Choline- and Folate-Deficient Diet,” Toxicology and Applied Pharmacology 262, no. 1 (2012): 52–59.
|
| [143] |
D. Weil, V. Di Martino, G. Mourey, et al., “Small Annexin V-Positive Platelet-Derived Microvesicles Affect Prognosis in Cirrhosis: A Longitudinal Study,” Clinical and Translational Gastroenterology 12, no. 5 (2021): e00333.
|
| [144] |
A. Payancé, G. Silva-Junior, J. Bissonnette, et al., “Hepatocyte Microvesicle Levels Improve Prediction of Mortality in Patients With Cirrhosis,” Hepatology 68, no. 4 (2018): 1508–1518.
|
| [145] |
Y. Nakao, P. Amrollahi, G. Parthasarathy, et al., “Circulating Extracellular Vesicles Are a Biomarker for NAFLD Resolution and Response to Weight Loss Surgery,” Nanomedicine: Nanotechnology, Biology and Medicine 36 (2021): 102430.
|
| [146] |
F. Santamaria-Martos, I. D. Benitez, J. Latorre, et al., “Comparative and Functional Analysis of Plasma Membrane-Derived Extracellular Vesicles From Obese Vs. Nonobese Women,” Clinical Nutrition 39, no. 4 (2020): 1067–1076.
|
| [147] |
Y. Wang, Y. Li, X. Wang, et al., “Circulating miR-130b Mediates Metabolic Crosstalk Between Fat and Muscle in Overweight/Obesity,” Diabetologia 56, no. 10 (2013): 2275–2285.
|
| [148] |
S. Y. Dang, Y. Leng, Z. X. Wang, et al., “Exosomal Transfer of Obesity Adipose Tissue for Decreased miR-141-3p Mediate Insulin Resistance of Hepatocytes,” International Journal of Biological Sciences 15, no. 2 (2019): 351–368.
|
| [149] |
M. E. Kranendonk, D. P. de Kleijn, E. Kalkhoven, et al., “Extracellular Vesicle Markers in Relation to Obesity and Metabolic Complications in Patients With Manifest Cardiovascular Disease,” Cardiovascular Diabetology 13 (2014): 37.
|
| [150] |
B. B. Brandao, M. Lino, and C. R. Kahn, “Extracellular miRNAs as Mediators of Obesity-Associated Disease,” Journal of Physiology 600, no. 5 (2022): 1155–1169.
|
| [151] |
M. J. Hubal, E. P. Nadler, S. C. Ferrante, et al., “Circulating Adipocyte-Derived Exosomal MicroRNAs Associated With Decreased Insulin Resistance After Gastric Bypass,” Obesity 25, no. 1 (2017): 102–110.
|
| [152] |
X. Yu, S. Lei, Y. Shen, et al., “Cholesterol Sulfate: Pathophysiological Implications and Potential Therapeutics,” Biomolecules 15, no. 5 (2025): 646.
|
| [153] |
R. H. J. A. Slart, M. Punda, D. S. Ali, et al., “Updated Practice Guideline for Dual-Energy X-Ray Absorptiometry (DXA),” European Journal of Nuclear Medicine and Molecular Imaging 52, no. 2 (2025): 539–563.
|
| [154] |
Y. Zhang, F. Cai, J. Liu, et al., “Transfer RNA-Derived Fragments as Potential Exosome tRNA-Derived Fragment Biomarkers for Osteoporosis,” International Journal of Rheumatic Diseases 21, no. 9 (2018): 1659–1669.
|
| [155] |
M. Chen, Y. Li, H. Lv, P. Yin, L. Zhang, and P. Tang, “Quantitative Proteomics and Reverse Engineer Analysis Identified Plasma Exosome Derived Protein Markers Related to Osteoporosis,” Journal of Proteomics 228 (2020): 103940.
|
| [156] |
F. Zhi, Y. Ding, R. Wang, Y. Yang, K. Luo, and F. Hua, “Exosomal hsa_circ_0006859 Is a Potential Biomarker for Postmenopausal Osteoporosis and Enhances Adipogenic Versus Osteogenic Differentiation in Human Bone Marrow Mesenchymal Stem Cells by Sponging miR-431-5p,” Stem Cell Research & Therapy 12, no. 1 (2021): 157.
|
| [157] |
J. S. Tang, H. X. Yu, R. X. Ruan, R. Chen, and Z. Zhu, “LncRNA SNHG14 Delivered by Bone Marrow Mesenchymal Stem Cells-Secreted Exosomes Regulates Osteogenesis and Adipogenesis in Osteoporosis by Mediating the miR-27a-3p/LMNB1 Axis,” Kaohsiung Journal of Medical Sciences 41, no. 5 (2025): e70004.
|
| [158] |
Z. Wang, J. Zhang, S. Zhang, et al., “MiR‑30e and miR‑92a Are Related to Atherosclerosis by Targeting ABCA1,” Molecular Medicine Reports 19, no. 4 (2019): 3298–3304.
|
| [159] |
Y. Xing and X. Lin, “Challenges and Advances in the Management of Inflammation in Atherosclerosis,” Journal of Advanced Research 71 (2025): 317–335.
|
| [160] |
Z. Su, Y. Li, J. C. James, et al., “Quantitative Trait Locus Analysis of Atherosclerosis in an Intercross Between C57BL/6 and C3H Mice Carrying the Mutant Apolipoprotein E Gene,” Genetics 172, no. 3 (2006): 1799–1807.
|
| [161] |
Q. Li, Q. Feng, H. Zhou, et al., “Mechanisms and Therapeutic Strategies of Extracellular Vesicles in Cardiovascular Diseases,” Medcomm 4, no. 6 (2023): e454.
|
| [162] |
J. Zhu, B. Liu, Z. Wang, et al., “Exosomes From Nicotine-Stimulated Macrophages Accelerate Atherosclerosis Through miR-21-3p/PTEN-mediated VSMC Migration and Proliferation,” Theranostics 9, no. 23 (2019): 6901–6919.
|
| [163] |
N. Satyadev, M. I. Rivera, N. K. Nikolov, and A. Fakoya, “Exosomes as Biomarkers and Therapy in Type 2 Diabetes Mellitus and Associated Complications,” Frontiers in Physiology 14 (2023): 1241096.
|
| [164] |
I. Vukelić, B. Šuša, S. Klobučar, et al., “Exosome-Derived MicroRNAs: Bridging the Gap Between Obesity and Type 2 Diabetes in Diagnosis and Treatment,” Diabetology 5, no. 7 (2024): 706–724.
|
| [165] |
J. B. Simonsen, “Lipid Nanoparticle-Based Strategies for Extrahepatic Delivery of Nucleic Acid Therapies-Challenges and Opportunities,” Journal of Controlled Release 370 (2024): 763–772.
|
| [166] |
S. Sen, J. Xavier, N. Kumar, M. Z. Ahmad, and O. P. Ranjan, “Exosomes as Natural Nanocarrier-Based Drug Delivery System: Recent Insights and Future Perspectives,” 3 Biotech 13, no. 3 (2023): 101.
|
| [167] |
Z. Nouri, A. Barfar, S. Perseh, et al., “Exosomes as Therapeutic and Drug Delivery Vehicle for Neurodegenerative Diseases,” Journal of Nanobiotechnology 22, no. 1 (2024): 463.
|
| [168] |
S. Sadeghi, F. R. Tehrani, S. Tahmasebi, A. Shafiee, and S. M. Hashemi, “Exosome Engineering in Cell Therapy and Drug Delivery,” Inflammopharmacology 31, no. 1 (2023): 145–169.
|
| [169] |
M. Zhuang, D. Du, L. Pu, et al., “SPION-Decorated Exosome Delivered BAY55-9837 Targeting the Pancreas Through Magnetism to Improve the Blood GLC Response,” Small 15, no. 52 (2019): e1903135.
|
| [170] |
J. Driscoll, C. Wehrkamp, Y. Ota, J. N. Thomas, I. K. Yan, and T. Patel, “Biological Nanotherapeutics for Liver Disease,” Hepatology 74, no. 5 (2021): 2863–2875.
|
| [171] |
K. Tang, Y. Zhang, H. Zhang, et al., “Delivery of Chemotherapeutic Drugs in Tumour Cell-Derived Microparticles,” Nature Communications 3 (2012): 1282.
|
| [172] |
O. M. Saka, D. D. Dora, G. Kibar, and A. Tevlek, “Expanding the Role of Exosomes in Drug, Biomolecule, and Nanoparticle Delivery,” Life Sciences 368 (2025): 123499.
|
| [173] |
A. H. Aghayan, Y. Mirazimi, K. Fateh, A. Keshtkar, M. Rafiee, and A. Atashi, “Therapeutic Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Sepsis: A Systematic Review and Meta-Analysis of Preclinical Studies,” Stem Cell Reviews and Reports 20, no. 6 (2024): 1480–1500.
|
| [174] |
X. Feng, H. Zhang, S. Yang, et al., “From Stem Cells to Pancreatic β-Cells: Strategies, Applications, and Potential Treatments for Diabetes,” Molecular and Cellular Biochemistry 480, no. 1 (2025): 173–190.
|
| [175] |
S. K. Yap, K. L. Tan, N. Y. Abd Rahaman, et al., “Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorated Insulin Resistance in Type 2 Diabetes Mellitus Rats,” Pharmaceutics 14, no. 3 (2022): 649.
|
| [176] |
H. Zhao, Q. Shang, Z. Pan, et al., “Exosomes From Adipose-Derived Stem Cells Attenuate Adipose Inflammation and Obesity Through Polarizing M2 Macrophages and Beiging in White Adipose Tissue,” Diabetes 67, no. 2 (2018): 235–247.
|
| [177] |
X. Hou, S. Yin, R. Ren, et al., “Myeloid-Cell-Specific IL-6 Signaling Promotes MicroRNA-223-Enriched Exosome Production to Attenuate NAFLD-Associated Fibrosis,” Hepatology 74, no. 1 (2021): 116–132.
|
| [178] |
A. Eguchi, M. Iwasa, and H. Nakagawa, “Extracellular Vesicles in Fatty Liver Disease and Steatohepatitis: Role as Biomarkers and Therapeutic Targets,” Liver International 43, no. 2 (2023): 292–298.
|
| [179] |
L. Cheng, P. Yu, F. Li, et al., “Human Umbilical Cord-Derived Mesenchymal Stem Cell-Exosomal miR-627-5p Ameliorates Non-Alcoholic Fatty Liver Disease by Repressing FTO Expression,” Human Cell 34, no. 6 (2021): 1697–1708.
|
| [180] |
Y. Wang, M. Li, L. Chen, et al., “Natural Killer Cell-Derived Exosomal miR-1249-3p Attenuates Insulin Resistance and Inflammation in Mouse Models of Type 2 Diabetes,” Signal Transduction and Targeted Therapy 6, no. 1 (2021): 409.
|
| [181] |
M. O. El-Derany and S. G. AbdelHamid, “Upregulation of miR-96-5p by Bone Marrow Mesenchymal Stem Cells and Their Exosomes Alleviate Non-Alcoholic Steatohepatitis: Emphasis on Caspase-2 Signaling Inhibition,” Biochemical Pharmacology 190 (2021): 114624.
|
| [182] |
D. Povero, E. M. Pinatel, A. Leszczynska, et al., “Human Induced Pluripotent Stem Cell-Derived Extracellular Vesicles Reduce Hepatic Stellate Cell Activation and Liver Fibrosis,” JCI Insight 4, no. 14 (2019): e125652.
|
| [183] |
X. Rong, J. Liu, X. Yao, T. Jiang, Y. Wang, and F. Xie, “Human Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Alleviate Liver Fibrosis Through the Wnt/β-Catenin Pathway,” Stem Cell Research & Therapy 10 (2019): 98.
|
| [184] |
X. Li, R. Chen, S. Kemper, and D. R. Brigstock, “Extracellular Vesicles From Hepatocytes Are Therapeutic for Toxin-Mediated Fibrosis and Gene Expression in the Liver,” Frontiers in Cell and Developmental Biology 7 (2020): 368.
|
| [185] |
E. Fiore, L. M. Domínguez, J. Bayo, et al., “Human Umbilical Cord Perivascular Cells-Derived Extracellular Vesicles Mediate the Transfer of IGF-I to the Liver and Ameliorate Hepatic Fibrogenesis in Mice,” Gene Therapy 27, no. 1–2 (2020): 62–73.
|
| [186] |
H. Haga, I. K. Yan, K. Takahashi, A. Matsuda, and T. Patel, “Extracellular Vesicles From Bone Marrow-Derived Mesenchymal Stem Cells Improve Survival From Lethal Hepatic Failure in Mice,” Stem Cells Translational Medicine 6, no. 4 (2017): 1262–1272.
|
| [187] |
C. Y. Tan, R. C. Lai, W. Wong, Y. Y. Dan, S. K. Lim, and H. K. Ho, “Mesenchymal Stem Cell-Derived Exosomes Promote Hepatic Regeneration in Drug-Induced Liver Injury Models,” Stem Cell Research & Therapy 5 (2014): 76.
|
| [188] |
F. Anger, M. Camara, E. Ellinger, et al., “Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Improve Liver Regeneration After Ischemia Reperfusion Injury in Mice,” Stem Cells and Development 28, no. 21 (2019): 1451–1462.
|
| [189] |
F. Sun, Y. Sun, F. Wu, W. Xu, and H. Qian, “Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapy for Diabetes Mellitus and Diabetic Complications,” Pharmaceutics 14, no. 10 (2022): 2208.
|
| [190] |
Y. Song, Y. You, X. Xu, et al., “Adipose-Derived Mesenchymal Stem Cell-Derived Exosomes Biopotentiated Extracellular Matrix Hydrogels Accelerate Diabetic Wound Healing and Skin Regeneration,” Advanced Science 10, no. 30 (2023): e2304023.
|
| [191] |
L. Bouchareychas, P. Duong, S. Covarrubias, et al., “Macrophage Exosomes Resolve Atherosclerosis by Regulating Hematopoiesis and Inflammation via MicroRNA Cargo,” Cell Reports 32, no. 2 (2020): 107881.
|
| [192] |
J. Liu, W. Li, Y. Bian, et al., “Garlic-Derived Exosomes Regulate PFKFB3 Expression to Relieve Liver Dysfunction in High-Fat Diet-Fed Mice via Macrophage-Hepatocyte Crosstalk,” Phytomedicine 112 (2023): 154679.
|
| [193] |
Z. Li, Y. Du, Y. Lu, et al., “Hypericum perforatum-Derived Exosomes-Like Nanovesicles for Adipose Tissue Photodynamic Therapy,” Phytomedicine 132 (2024): 155854.
|
| [194] |
M. Casajuana Ester and R. M. Day, “Production and Utility of Extracellular Vesicles With 3D Culture Methods,” Pharmaceutics 15, no. 2 (2023): 663.
|
| [195] |
M. Chen, Y. Zhao, L. Zhou, et al., “Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Enhance Insulin Sensitivity in Insulin Resistant Human Adipocytes,” Current Medical Science 41, no. 1 (2021): 87–93.
|
| [196] |
Q. Niu, T. Wang, Z. Wang, et al., “Adipose-Derived Mesenchymal Stem Cell-Secreted Extracellular Vesicles Alleviate Non-Alcoholic Fatty Liver Disease via Delivering miR-223-3p,” Adipocyte 11, no. 1 (2022): 572–587.
|
| [197] |
F. Sani, M. Soufi Zomorrod, N. Azarpira, et al., “The Effect of Mesenchymal Stem Cell-Derived Exosomes and miR17-5p Inhibitor on Multicellular Liver Fibrosis Microtissues,” Stem Cells International 2023 (2023): 8836452.
|
| [198] |
F. Xu, C. Xia, L. Dou, and X. Huang, “Knowledge Mapping of Exosomes in Metabolic Diseases: A Bibliometric Analysis (2007–2022),” Frontiers in Endocrinology 14 (2023): 1176430.
|
| [199] |
P. Ranjan, K. Colin, R. K. Dutta, and S. K. Verma, “Challenges and Future Scope of Exosomes in the Treatment of Cardiovascular Diseases,” Journal of Physiology 601, no. 22 (2023): 4873–4893.
|
| [200] |
J. Mleczko, F. J. Ortega, J. M. Falcon-Perez, M. Wabitsch, J. M. Fernandez-Real, and S. Mora, “Extracellular Vesicles From Hypoxic Adipocytes and Obese Subjects Reduce Insulin-Stimulated Glucose Uptake,” Molecular Nutrition & Food Research 62, no. 5 (2018): 1700917.
|
| [201] |
J. Rezaie, M. Feghhi, and T. Etemadi, “A Review on Exosomes Application in Clinical Trials: Perspective, Questions, and Challenges,” Cell Communication and Signaling 20, no. 1 (2022): 145.
|
| [202] |
A. Anwar, S. Rana, and P. Pathak, “Artificial Intelligence in the Management of Metabolic Disorders: A Comprehensive Review,” Journal of Endocrinological Investigation 48, no. 7 (2025): 1525–1538.
|
| [203] |
M. Yi, Y. Liu, and Z. Su, “AlphaMissense, a Groundbreaking Advancement in Artificial Intelligence for Predicting the Effects of Missense Variants,” MedComm-Future Medicine 3, no. e70 (2024): e70.
|
| [204] |
H. S. Chahar, T. Corsello, A. S. Kudlicki, N. Komaravelli, and A. Casola, “Respiratory Syncytial Virus Infection Changes Cargo Composition of Exosome Released From Airway Epithelial Cells,” Scientific Reports 8 (2018): 387.
|
| [205] |
R. Dhar, S. Gorai, A. Devi, R. Muthusamy, A. Alexiou, and M. Papadakis, “Decoding of Exosome Heterogeneity for Cancer Theranostics,” Clinical and Translational Medicine 13, no. 6 (2023): e1288.
|
| [206] |
G. Zhang, S. Cen, X. Huang, et al., “Size Matters: Curvature and Antigen-Mediated Dual Recognition of Size-Specific Tumor-Derived Exosomes,” Analytical Chemistry 96, no. 44 (2024): 17897–17906.
|
| [207] |
G. K. Patel, M. A. Khan, H. Zubair, et al., “Comparative Analysis of Exosome Isolation Methods Using Culture Supernatant for Optimum Yield, Purity and Downstream Applications,” Scientific Reports 9 (2019): 5335.
|
| [208] |
H. Im, K. Lee, R. Weissleder, H. Lee, and C. M. Castro, “Novel Nanosensing Technologies for Exosome Detection and Profiling,” Lab on a Chip 17, no. 17 (2017): 2892–2898.
|
| [209] |
Y. Lei, X. Fei, Y. Ding, et al., “Simultaneous Subset Tracing and miRNA Profiling of Tumor-Derived Exosomes via Dual-Surface-Protein Orthogonal Barcoding,” Science Advances 9, no. 40 (2023): eadi1556.
|
| [210] |
H. B. Koh, H. J. Kim, S. W. Kang, and T. H. Yoo, “Exosome-Based Drug Delivery: Translation From Bench to Clinic,” Pharmaceutics 15, no. 8 (2023): 2042.
|
RIGHTS & PERMISSIONS
2025 The Author(s). MedComm - Future Medicine published by John Wiley & Sons Australia, Ltd on behalf of Sichuan International Medical Exchange & Promotion Association (SCIMEA).