REFERENCES
1. Sharma S, Le Guillou D, Chen JY. Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis. Nat Rev Gastroenterol Hepatol. 2023;20:662-78.
2. Airola C, Pallozzi M, Cerrito L, et al. Microvascular thrombosis and liver fibrosis progression: mechanisms and clinical applications. Cells. 2023;12:1712.
3. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77:1797-835.
4. Ebrahimi H, Naderian M, Sohrabpour AA. New concepts on reversibility and targeting of liver fibrosis; a review article. Middle East J Dig Dis. 2018;10:133-48.
5. Bruno S, Chiabotto G, Camussi G. Extracellular vesicles: a therapeutic option for liver fibrosis. Int J Mol Sci. 2020;21:4255.
6. Wiklander OPB, Brennan MÁ, Lötvall J, Breakefield XO, El Andaloussi S. Advances in therapeutic applications of extracellular vesicles. Sci Transl Med. 2019;11:eaav8521.
7. Chong SY, Lee CK, Huang C, et al. Extracellular vesicles in cardiovascular diseases: alternative biomarker sources, therapeutic agents, and drug delivery carriers. Int J Mol Sci. 2019;20:3272.
8. de Jong OG, Kooijmans SAA, Murphy DE, et al. Drug delivery with extracellular vesicles: from imagination to innovation. Acc Chem Res. 2019;52:1761-70.
9. Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9:581-93.
10. Welsh JA, Goberdhan DCI, O’Driscoll L, et al; MISEV Consortium. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J Extracell Vesicles. 2024;13:e12404.
11. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367:eaau6977.
12. Mori MA, Ludwig RG, Garcia-Martin R, Brandão BB, Kahn CR. Extracellular miRNAs: from biomarkers to mediators of physiology and disease. Cell Metab. 2019;30:656-73.
13. Ogawa R, Tanaka C, Sato M, et al. Adipocyte-derived microvesicles contain RNA that is transported into macrophages and might be secreted into blood circulation. Biochem Biophys Res Commun. 2010;398:723-9.
14. Simons M, Raposo G. Exosomes--vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009;21:575-81.
15. Sarvar D, Shamsasenjan K, Akbarzadehlaleh P. Mesenchymal stem cell-derived exosomes: new opportunity in cell-free therapy. Adv Pharm Bull. 2016;6:293-9.
16. Berumen J, Baglieri J, Kisseleva T, Mekeel K. Liver fibrosis: pathophysiology and clinical implications. WIREs Mech Dis. 2021;13:e1499.
17. Stalnikowitz D, Weissbrod AB. Liver fibrosis and inflammation. A review. Ann Hepatol. 2003;2:159-63.
18. Tanaka M, Miyajima A. Liver regeneration and fibrosis after inflammation. Inflamm Regen. 2016;36:19.
19. Garbuzenko DV. Pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis. World J Clin Cases. 2022;10:3662-76.
20. Cai X, Wang J, Wang J, et al. Intercellular crosstalk of hepatic stellate cells in liver fibrosis: new insights into therapy. Pharmacol Res. 2020;155:104720.
21. Matsuda M, Seki E. Hepatic stellate cell-macrophage crosstalk in liver fibrosis and carcinogenesis. Semin Liver Dis. 2020;40:307-20.
22. Roehlen N, Crouchet E, Baumert TF. Liver fibrosis: mechanistic concepts and therapeutic perspectives. Cells. 2020;9:875.
23. Iredale JP, Thompson A, Henderson NC. Extracellular matrix degradation in liver fibrosis: biochemistry and regulation. Biochim Biophys Acta. 2013;1832:876-83.
24. Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014;15:786-801.
25. Saki S, Monjezi S, Ghaffari F, et al. Unraveling the exosome-miR-133a axis: targeting TGF-β signaling via WJ-MSC-derived exosomes for anti-fibrotic therapy in liver fibrosis. Iran Biomed J. 2024;28:235-44.
26. Afarin R, Behdarvand T, Shakerian E, Salehipour Bavarsad S, Rashidi M. Exosomes of Whartons’ jelly mesenchymal stem cell reduce the NOX genes in TGF-β-induced hepatic fibrosis. Iran J Basic Med Sci. 2022;25:1498-503.
27. Rashidi M, Matour E, Monjezi S, et al. Effects of exosomes of mesenchymal stem cells on cholesterol-induced hepatic fibrogenesis. Iran J Basic Med Sci. 2023;26:695-700.
28. Torabi S, Zarrabi M, Shekari F, et al. Wharton’s Jelly mesenchymal stem cell-derived extracellular vesicles induce liver fibrosis-resolving phenotype in alternatively activated macrophages. J Cell Mol Med. 2024;28:e18507.
29. Zong R, Zheng Y, Yan Y, et al. Mesenchymal stem cells-derived exosomes alleviate liver fibrosis by targeting Hedgehog/SMO signaling. Hepatol Int. 2024;18:1781-91.
30. Li T, Yan Y, Wang B, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev. 2013;22:845-54.
31. Yuan M, Yao L, Chen P, et al. Human umbilical cord mesenchymal stem cells inhibit liver fibrosis via the microRNA-148a-5p/SLIT3 axis. Int Immunopharmacol. 2023;125:111134.
32. Cheng F, Yang F, Wang Y, Zhou J, Qian H, Yan Y. Mesenchymal stem cell-derived exosomal miR-27b-3p alleviates liver fibrosis via downregulating YAP/LOXL2 pathway. J Nanobiotechnology. 2023;21:195.
33. Wang Y, Wang C, Yang F, et al. USP9X-enriched MSC-sEV inhibits LSEC angiogenesis in MASH mice by downregulating the IκBα/NF-κB/Ang-2 pathway. Pharmacol Res. 2024;209:107471.
34. Dong L, Pu Y, Chen X, et al. hUCMSC-extracellular vesicles downregulated hepatic stellate cell activation and reduced liver injury in S. japonicum-infected mice. Stem Cell Res Ther. 2020;11:21.
35. Huang YJ, Cao J, Lee CY, Wu YM. Umbilical cord blood plasma-derived exosomes as a novel therapy to reverse liver fibrosis. Stem Cell Res Ther. 2021;12:568.
36. Jiang W, Tan Y, Cai M, et al. Human umbilical cord MSC-derived exosomes suppress the development of CCl4-induced liver injury through antioxidant effect. Stem Cells Int. 2018;2018:6079642.
37. Sani F, Soufi Zomorrod M, Azarpira N, Soleimani M. The effect of mesenchymal stem cell-derived exosomes and miR17-5p inhibitor on multicellular liver fibrosis microtissues. Stem Cells Int. 2023;2023:8836452.
38. Chiabotto G, Semnani A, Ceccotti E, Guenza M, Camussi G, Bruno S. Mesenchymal stromal cell-derived extracellular vesicles for reversing hepatic fibrosis in 3D liver spheroids. Biomedicines. 2024;12:1849.
39. Tan Y, Huang Y, Mei R, et al. HucMSC-derived exosomes delivered BECN1 induces ferroptosis of hepatic stellate cells via regulating the xCT/GPX4 axis. Cell Death Dis. 2022;13:319.
40. Tian S, Zhou X, Zhang M, et al. Mesenchymal stem cell-derived exosomes protect against liver fibrosis via delivering miR-148a to target KLF6/STAT3 pathway in macrophages. Stem Cell Res Ther. 2022;13:330.
41. Shi Y, Yang X, Wang S, et al. Human umbilical cord mesenchymal stromal cell-derived exosomes protect against MCD-induced NASH in a mouse model. Stem Cell Res Ther. 2022;13:517.
42. Zheng W, Bian S, Qiu S, et al. Placenta mesenchymal stem cell-derived extracellular vesicles alleviate liver fibrosis by inactivating hepatic stellate cells through a miR-378c/SKP2 axis. Inflamm Regen. 2023;43:47.
43. Alhomrani M, Correia J, Zavou M, et al. The human amnion epithelial cell secretome decreases hepatic fibrosis in mice with chronic liver fibrosis. Front Pharmacol. 2017;8:748.
44. Ohara M, Ohnishi S, Hosono H, et al. Extracellular vesicles from amnion-derived mesenchymal stem cells ameliorate hepatic inflammation and fibrosis in rats. Stem Cells Int. 2018;2018:3212643.
45. Xu AL, Han L, Yan J, Liu D, Wang W. Effects of mesenchymal stem cells-derived extracellular vesicles on inhibition of hepatic fibrosis by delivering miR-200a. Tissue Eng Regen Med. 2024;21:609-24.
46. Wang N, Li X, Zhong Z, et al. 3D hESC exosomes enriched with miR-6766-3p ameliorates liver fibrosis by attenuating activated stellate cells through targeting the TGFβRII-SMADS pathway. J Nanobiotechnology. 2021;19:437.
47. Rong X, Liu J, Yao X, Jiang T, Wang Y, Xie F. Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/β-catenin pathway. Stem Cell Res Ther. 2019;10:98.
48. Rostom DM, Attia N, Khalifa HM, Abou Nazel MW, El Sabaawy EA. The therapeutic potential of extracellular vesicles versus mesenchymal stem cells in liver damage. Tissue Eng Regen Med. 2020;17:537-52.
49. Sun C, Shi C, Duan X, Zhang Y, Wang B. Exosomal microRNA-618 derived from mesenchymal stem cells attenuate the progression of hepatic fibrosis by targeting Smad4. Bioengineered. 2022;13:5915-27.
50. Ma J, Li Y, Chen M, et al. hMSCs-derived exosome circCDK13 inhibits liver fibrosis by regulating the expression of MFGE8 through miR-17-5p/KAT2B. Cell Biol Toxicol. 2023;39:1-22.
51. An SY, Jang YJ, Lim HJ, et al. Milk fat globule-EGF factor 8, secreted by mesenchymal stem cells, protects against liver fibrosis in mice. Gastroenterology. 2017;152:1174-86.
52. Didamoony MA, Atwa AM, Ahmed LA. Modulatory effect of rupatadine on mesenchymal stem cell-derived exosomes in hepatic fibrosis in rats: a potential role for miR-200a. Life Sci. 2023;324:121710.
53. Zhao S, Liu Y, Pu Z. Bone marrow mesenchymal stem cell-derived exosomes attenuate D-GaIN/LPS-induced hepatocyte apoptosis by activating autophagy in vitro. Drug Des Devel Ther. 2019;13:2887-97.
54. Zhang Y, Zhangdi H, Nie X, et al. Exosomes derived from BMMSCs mitigate the hepatic fibrosis via anti-pyroptosis pathway in a cirrhosis model. Cells. 2022;11:4004.
55. Feng X, Feng B, Zhou J, et al. Mesenchymal stem cells alleviate mouse liver fibrosis by inhibiting pathogenic function of intrahepatic B cells. Hepatology. 2025;81:1211-27.
56. Ellakany AR, El Baz H, Shoheib ZS, Elzallat M, Ashour DS, Yassen NA. Stem cell-derived exosomes as a potential therapy for schistosomal hepatic fibrosis in experimental animals. Pathog Glob Health. 2024;118:429-49.
57. Han HS, Lee H, You D, et al. Human adipose stem cell-derived extracellular nanovesicles for treatment of chronic liver fibrosis. J Control Release. 2020;320:328-36.
58. Zhang Z, Shang J, Yang Q, et al. Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism. J Nanobiotechnology. 2023;21:29.
59. Al Saihati HA, Badr OA, Dessouky AA, et al. Exploring the cytoprotective role of mesenchymal stem cell-derived exosomes in chronic liver fibrosis: insights into the Nrf2/Keap1/p62 signaling pathway. Int Immunopharmacol. 2024;141:112934.
60. Wu B, Feng J, Guo J, et al. ADSCs-derived exosomes ameliorate hepatic fibrosis by suppressing stellate cell activation and remodeling hepatocellular glutamine synthetase-mediated glutamine and ammonia homeostasis. Stem Cell Res Ther. 2022;13:494.
61. Du Z, Wu T, Liu L, Luo B, Wei C. Extracellular vesicles-derived miR-150-5p secreted by adipose-derived mesenchymal stem cells inhibits CXCL1 expression to attenuate hepatic fibrosis. J Cell Mol Med. 2021;25:701-15.
62. Gan L, Zheng L, Yao L, et al. Exosomes from adipose-derived mesenchymal stem cells improve liver fibrosis by regulating the miR-20a-5p/TGFBR2 axis to affect the p38 MAPK/NF-κB pathway. Cytokine. 2023;172:156386.
63. Takeda N, Tsuchiya A, Mito M, et al. Analysis of distribution, collection, and confirmation of capacity dependency of small extracellular vesicles toward a therapy for liver cirrhosis. Inflamm Regen. 2023;43:48.
64. Watanabe T, Tsuchiya A, Takeuchi S, et al. Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles. Regen Ther. 2020;14:252-61.
65. Kim J, Lee C, Shin Y, et al. sEVs from tonsil-derived mesenchymal stromal cells alleviate activation of hepatic stellate cells and liver fibrosis through miR-486-5p. Mol Ther. 2021;29:1471-86.
66. Bruno S, Pasquino C, Herrera Sanchez MB, et al. HLSC-derived extracellular vesicles attenuate liver fibrosis and inflammation in a murine model of non-alcoholic steatohepatitis. Mol Ther. 2020;28:479-89.
67. Chiabotto G, Ceccotti E, Pasquino C, et al. Human liver stem cell-derived extracellular vesicles modulate long non-coding RNA expression profile in an in vivo model of non-alcoholic steatohepatitis. Explor Dig Dis. 2023;2:172-87.
68. Chiabotto G, Ceccotti E, Tapparo M, Camussi G, Bruno S. Human liver stem cell-derived extracellular vesicles target hepatic stellate cells and attenuate their pro-fibrotic phenotype. Front Cell Dev Biol. 2021;9:777462.
69. Hu Z, Zhao Y, Jiang J, et al. Exosome-derived miR-142-5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB. Environ Toxicol. 2023;38:1860-73.
70. Frangogiannis N. Transforming growth factor-β in tissue fibrosis. J Exp Med. 2020;217:e20190103.
71. Carthy JM. TGFβ signaling and the control of myofibroblast differentiation: implications for chronic inflammatory disorders. J Cell Physiol. 2018;233:98-106.
72. Russo E, Alberti G, Corrao S, et al. The truth is out there: biological features and clinical indications of extracellular vesicles from human perinatal stem cells. Cells. 2023;12:2347.
73. Hazrati A, Malekpour K, Soudi S, Hashemi SM. Mesenchymal stromal/stem cells and their extracellular vesicles application in acute and chronic inflammatory liver diseases: emphasizing on the anti-fibrotic and immunomodulatory mechanisms. Front Immunol. 2022;13:865888.
74. Tan CY, Lai RC, Wong W, Dan YY, Lim SK, Ho HK. Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther. 2014;5:76.
75. Gómez-Virgilio L, Silva-Lucero MD, Flores-Morelos DS, et al. Autophagy: a key regulator of homeostasis and disease: an overview of molecular mechanisms and modulators. Cells. 2022;11:2262.
76. Talukdar S, Das SK, Emdad L, Fisher PB. Autophagy and senescence: insights from normal and cancer stem cells. Adv Cancer Res. 2021;150:147-208.
77. Mao YQ, Fan XM. Autophagy: a new therapeutic target for liver fibrosis. World J Hepatol. 2015;7:1982-6.
78. Hazari Y, Bravo-San Pedro JM, Hetz C, Galluzzi L, Kroemer G. Autophagy in hepatic adaptation to stress. J Hepatol. 2020;72:183-96.
79. Wang C, Ma C, Gong L, et al. Macrophage polarization and its role in liver disease. Front Immunol. 2021;12:803037.
80. Arora S, Dev K, Agarwal B, Das P, Syed MA. Macrophages: their role, activation and polarization in pulmonary diseases. Immunobiology. 2018;223:383-96.
81. Xue JD, Gao J, Tang AF, Feng C. Shaping the immune landscape: multidimensional environmental stimuli refine macrophage polarization and foster revolutionary approaches in tissue regeneration. Heliyon. 2024;10:e37192.
82. Hu Q, Lyon CJ, Fletcher JK, Tang W, Wan M, Hu TY. Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses. Acta Pharm Sin B. 2021;11:1493-512.
83. Wang J, Wu Z, Xia M, et al. Extracellular vesicles derived from liver sinusoidal endothelial cells inhibit the activation of hepatic stellate cells and Kupffer cells in vitro. Biochim Biophys Acta Mol Basis Dis. 2024;1870:167020.
84. Chen L, Chen R, Kemper S, Brigstock DR. Pathways of production and delivery of hepatocyte exosomes. J Cell Commun Signal. 2018;12:343-57.
85. Li X, Chen R, Kemper S, Brigstock DR. Extracellular vesicles from hepatocytes are therapeutic for toxin-mediated fibrosis and gene expression in the liver. Front Cell Dev Biol. 2019;7:368.
86. Liu W, Wu J, Cao H, et al. Human-induced hepatocytes-derived extracellular vesicles ameliorated liver fibrosis in mice via suppression of TGF-β1/smad signaling and activation of Nrf2/HO-1 signaling. Stem Cells Dev. 2023;32:638-51.
87. Zhong Z, Cui XL, Tan KJ, et al. Apoptotic vesicles (apoVs) derived from fibroblast-converted hepatocyte-like cells effectively ameliorate liver fibrosis. J Nanobiotechnology. 2024;22:541.
88. 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;5:125652.
89. Wang L, Wang Y, Quan J. Exosomes derived from natural killer cells inhibit hepatic stellate cell activation and liver fibrosis. Hum Cell. 2020;33:582-9.
90. Chen L, Chen R, Kemper S, Cong M, You H, Brigstock DR. Therapeutic effects of serum extracellular vesicles in liver fibrosis. J Extracell Vesicles. 2018;7:1461505.
91. Maeda Y, Watanabe Y, Ishikawa N, et al. Platelet-rich plasma-derived extracellular vesicles improve liver cirrhosis in mice. Regen Ther. 2024;26:1048-57.
92. Reif S, Atias A, Musseri M, Koroukhov N, Gerstl RG. Beneficial effects of milk-derived extracellular vesicles on liver fibrosis progression by inhibiting hepatic stellate cell activation. Nutrients. 2022;14:4049.
93. Gong Q, Zeng Z, Jiang T, et al. Anti-fibrotic effect of extracellular vesicles derived from tea leaves in hepatic stellate cells and liver fibrosis mice. Front Nutr. 2022;9:1009139.
94. Kim JS, Eom JY, Kim HW, et al. Hemp sprout-derived exosome-like nanovesicles as hepatoprotective agents attenuate liver fibrosis. Biomater Sci. 2024;12:5361-71.
95. Keshavarz Azizi Raftar S, Ashrafian F, Yadegar A, et al. The protective effects of live and pasteurized akkermansia muciniphila and its extracellular vesicles against HFD/CCl4-induced liver injury. Microbiol Spectr. 2021;9:e0048421.
96. Xu F, Liu J, Deng J, et al. Rapid and high-efficiency generation of mature functional hepatocyte-like cells from adipose-derived stem cells by a three-step protocol. Stem Cell Res Ther. 2015;6:193.
97. Zhong Z, Du J, Zhu X, et al. Highly efficient conversion of mouse fibroblasts into functional hepatic cells under chemical induction. J Mol Cell Biol. 2024;15:mjad071.
98. Calzoni E, Bertoldi A, Cusumano G, Buratta S, Urbanelli L, et al. Plant-derived extracellular vesicles: natural nanocarriers for biotechnological drugs. Processes. 2024;12:2938.
99. Shao M, Jin X, Chen S, Yang N, Feng G. Plant-derived extracellular vesicles -a novel clinical anti-inflammatory drug carrier worthy of investigation. Biomed Pharmacother. 2023;169:115904.
100. Zhang S, Wang Q, Tan DEL, et al. Gut-liver axis: potential mechanisms of action of food-derived extracellular vesicles. J Extracell Vesicles. 2024;13:e12466.
101. Yang Y, Wu Y, Yang D, et al. Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles. Bioact Mater. 2023;27:98-112.
102. Bader AM, Klose K, Bieback K, et al. Hypoxic preconditioning increases survival and pro-angiogenic capacity of human cord blood mesenchymal stromal cells in vitro. PLoS One. 2015;10:e0138477.
103. Duijvestein M, Wildenberg ME, Welling MM, et al. Pretreatment with interferon-γ enhances the therapeutic activity of mesenchymal stromal cells in animal models of colitis. Stem Cells. 2011;29:1549-58.
104. François M, Romieu-Mourez R, Li M, Galipeau J. Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation. Mol Ther. 2012;20:187-95.
105. Noone C, Kihm A, English K, O’Dea S, Mahon BP. IFN-γ stimulated human umbilical-tissue-derived cells potently suppress NK activation and resist NK-mediated cytotoxicity in vitro. Stem Cells Dev. 2013;22:3003-14.
106. Ragni E, Perucca Orfei C, De Luca P, et al. Inflammatory priming enhances mesenchymal stromal cell secretome potential as a clinical product for regenerative medicine approaches through secreted factors and EV-miRNAs: the example of joint disease. Stem Cell Res Ther. 2020;11:165.
107. Lim J, Lee S, Ju H, et al. Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells. Int J Mol Med. 2017;40:739-47.
108. Lee S, Lim J, Lee JH, et al. Ascorbic acid 2-glucoside stably promotes the primitiveness of embryonic and mesenchymal stem cells through ten-eleven translocation- and cAMP-responsive element-binding protein-1-dependent mechanisms. Antioxid Redox Signal. 2020;32:35-59.
109. Kang H, Kim KH, Lim J, et al. The therapeutic effects of human mesenchymal stem cells primed with sphingosine-1 phosphate on pulmonary artery hypertension. Stem Cells Dev. 2015;24:1658-71.
110. Damasceno PKF, de Santana TA, Santos GC, et al. Genetic engineering as a strategy to improve the therapeutic efficacy of mesenchymal stem/stromal cells in regenerative medicine. Front Cell Dev Biol. 2020;8:737.
111. Chen S, Sun F, Qian H, Xu W, Jiang J. Preconditioning and engineering strategies for improving the efficacy of mesenchymal stem cell-derived exosomes in cell-free therapy. Stem Cells Int. 2022;2022:1779346.
112. Takeuchi S, Tsuchiya A, Iwasawa T, et al. Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis. NPJ Regen Med. 2021;6:19.
113. Bavarsad S, Jalali MT, Bijan Nejad D, Alypoor B, Babaahmadi Rezaei H, Mohammadtaghvaei N. TGFβ1-pretreated exosomes of wharton jelly mesenchymal stem cell as a therapeutic strategy for improving liver fibrosis. Hepat Mon. 2022;22:e123416.
114. Tawfeek GA, Kasem HA. Curcumin preconditioned mesenchymal stem cells derived exosomes transplantation ameliorate and protect against non- alcoholic steatohepatitis by regulation the expression of key genes of inflammation and oxidative stress. Transpl Immunol. 2023;78:101837.
115. Jiang X, Liu Z, You H, et al. Quercetin-primed BMSC-derived extracellular vesicles ameliorate chronic liver damage through miR-136-5p and GNAS/STAT3 signaling pathways. Int Immunopharmacol. 2024;142:113162.
116. Lang Z, Li Y, Lin L, et al. Hepatocyte-derived exosomal miR-146a-5p inhibits hepatic stellate cell EMT process: a crosstalk between hepatocytes and hepatic stellate cells. Cell Death Discov. 2023;9:304.
117. Chen L, Lu FB, Chen DZ, et al. BMSCs-derived miR-223-containing exosomes contribute to liver protection in experimental autoimmune hepatitis. Mol Immunol. 2018;93:38-46.
118. Tian X, Wu L, Li X, Zheng W, Zuo H, Song H. Exosomes derived from bone marrow mesenchymal stem cells alleviate biliary ischemia reperfusion injury in fatty liver transplantation by inhibiting ferroptosis. Mol Cell Biochem. 2024;479:881-94.
119. Xuan J, Xu H, Li H, et al. Extracellular vesicles from miR-148a-5p-enriched bone marrow mesenchymal stem cells relieve hepatic fibrosis by targeting Smad4. Mol Biotechnol. 2022;64:535-45.
120. Ma L, Wei J, Zeng Y, et al. Mesenchymal stem cell-originated exosomal circDIDO1 suppresses hepatic stellate cell activation by miR-141-3p/PTEN/AKT pathway in human liver fibrosis. Drug Deliv. 2022;29:440-53.
121. Qu Y, Zhang Q, Cai X, et al. Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation. J Cell Mol Med. 2017;21:2491-502.
122. Lou G, Yang Y, Liu F, et al. MiR-122 modification enhances the therapeutic efficacy of adipose tissue-derived mesenchymal stem cells against liver fibrosis. J Cell Mol Med. 2017;21:2963-73.
123. Yu L, Xue J, Wu Y, Zhou H. Therapeutic effect of exosomes derived from hepatocyte-growth-factor-overexpressing adipose mesenchymal stem cells on liver injury. Folia Histochem Cytobiol. 2023;61:160-71.
124. Wang J, Ye W, Jiang M, Zhou Y, Zheng J. Therapeutic potential of exosome derived from hepatocyte growth factor-overexpressing adipose mesenchymal stem cells in TGFβ1-stimulated hepatic stellate cells. Cytotechnology. 2024;76:217-29.
125. Domínguez LM, Bueloni B, Cantero MJ, et al. Chromatographic scalable method to isolate engineered extracellular vesicles derived from mesenchymal stem cells for the treatment of liver fibrosis in mice. Int J Mol Sci. 2023;24:9586.
126. Fiore E, Domínguez LM, Bayo J, 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 Ther. 2020;27:62-73.
127. Zhu D, Sun Z, Wei J, et al. BMP7-loaded human umbilical cord mesenchymal stem cell-derived small extracellular vesicles ameliorate liver fibrosis by targeting activated hepatic stellate cells. Int J Nanomedicine. 2024;19:3475-95.
128. Wang Y, Chen Y, Yang F, et al. MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression. J Zhejiang Univ Sci B. 2024;25:594-604.
129. Li T, Li X, Han G, et al. The therapeutic potential and clinical significance of exosomes as carriers of drug delivery system. Pharmaceutics. 2022;15:21.
130. Herrmann IK, Wood MJA, Fuhrmann G. Extracellular vesicles as a next-generation drug delivery platform. Nat Nanotechnol. 2021;16:748-59.
131. Xie H, Sun L, Zhang L, et al. Mesenchymal stem cell-derived microvesicles support ex vivo expansion of cord blood-derived CD34+ cells. Stem Cells Int. 2016;2016:6493241.
132. Azizsoltani A, Hatami B, Zali MR, Mahdavi V, Baghaei K, Alizadeh E. Obeticholic acid-loaded exosomes attenuate liver fibrosis through dual targeting of the FXR signaling pathway and ECM remodeling. Biomed Pharmacother. 2023;168:115777.
133. Niknam B, Baghaei K, Mahmoud Hashemi S, Hatami B, Reza Zali M, Amani D. Human Wharton’s jelly mesenchymal stem cells derived-exosomes enriched by miR-124 promote an anti-fibrotic response in an experimental model of liver fibrosis. Int Immunopharmacol. 2023;119:110294.
134. Tang M, Chen Y, Li B, et al. Therapeutic targeting of STAT3 with small interference RNAs and antisense oligonucleotides embedded exosomes in liver fibrosis. FASEB J. 2021;35:e21557.
135. Ashour AA, El-Kamel AH, Mehanna RA, Mourad G, Heikal LA. Luteolin-loaded exosomes derived from bone marrow mesenchymal stem cells: a promising therapy for liver fibrosis. Drug Deliv. 2022;29:3270-80.
136. Tang M, Guo C, Sun M, et al. Effective delivery of osteopontin small interference RNA using exosomes suppresses liver fibrosis via TGF-β1 signaling. Front Pharmacol. 2022;13:882243.
137. You DG, Oh BH, Nguyen VQ, et al. Vitamin A-coupled stem cell-derived extracellular vesicles regulate the fibrotic cascade by targeting activated hepatic stellate cells in vivo. J Control Release. 2021;336:285-95.
138. Yang H, Wang W, Xiao J, et al. ROS-responsive injectable hydrogels loaded with exosomes carrying miR-4500 reverse liver fibrosis. Biomaterials. 2025;314:122887.
139. Luo N, Li J, Chen Y, et al. Hepatic stellate cell reprogramming via exosome-mediated CRISPR/dCas9-VP64 delivery. Drug Deliv. 2021;28:10-8.
140. Wan T, Zhong J, Pan Q, Zhou T, Ping Y, Liu X. Exosome-mediated delivery of Cas9 ribonucleoprotein complexes for tissue-specific gene therapy of liver diseases. Sci Adv. 2022;8:eabp9435.
141. Zhao Y, Yu Y, Wang S, Li J, Teng L. Small extracellular vesicles encapsulating lefty1 mRNA inhibit hepatic fibrosis. Asian J Pharm Sci. 2022;17:630-40.
142. Yu F, Liu Z, Feng J, et al. Hyaluronic acid modified extracellular vesicles targeting hepatic stellate cells to attenuate hepatic fibrosis. Eur J Pharm Sci. 2024;198:106783.
143. Gong L, Zhou H, Zhang S, et al. CD44-targeting drug delivery system of exosomes loading forsythiaside a combats liver fibrosis via regulating NLRP3-mediated pyroptosis. Adv Healthc Mater. 2023;12:e2202228.
144. Gong L, Zhou H, Zhang Y, et al. Preparation of phillygenin-hyaluronic acid composite milk-derived exosomes and its anti-hepatic fibrosis effect. Mater Today Bio. 2023;23:100804.
145. Albaladejo-García V, Morán L, Santos-Coquillat A, et al. Curcumin encapsulated in milk small extracellular vesicles as a nanotherapeutic alternative in experimental chronic liver disease. Biomed Pharmacother. 2024;173:116381.
146. Zhang G, Huang X, Xiu H, et al. Extracellular vesicles: natural liver-accumulating drug delivery vehicles for the treatment of liver diseases. J Extracell Vesicles. 2020;10:e12030.
147. Cecchin R, Troyer Z, Witwer K, Morris KV. Extracellular vesicles: the next generation in gene therapy delivery. Mol Ther. 2023;31:1225-30.
148. Hu C, Zhao L, Zhang L, Bao Q, Li L. Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury. Stem Cell Res Ther. 2020;11:377.
149. Chakraborty D, Šumová B, Mallano T, et al. Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis. Nat Commun. 2017;8:1130.
150. Xiang DM, Sun W, Ning BF, et al. The HLF/IL-6/STAT3 feedforward circuit drives hepatic stellate cell activation to promote liver fibrosis. Gut. 2018;67:1704-15.
151. Li J, Li X, Xu W, et al. Antifibrotic effects of luteolin on hepatic stellate cells and liver fibrosis by targeting AKT/mTOR/p70S6K and TGFβ/Smad signalling pathways. Liver Int. 2015;35:1222-33.
152. Cummins CB, Wang X, Nunez Lopez O, et al. Luteolin-mediated inhibition of hepatic stellate cell activation via suppression of the STAT3 pathway. Int J Mol Sci. 2018;19:1567.
153. Lorena D, Darby IA, Gadeau AP, et al. Osteopontin expression in normal and fibrotic liver. altered liver healing in osteopontin-deficient mice. J Hepatol. 2006;44:383-90.
154. Tang M, Jia H, Chen S, et al. Significance of MR/OPN/HMGB1 axis in NAFLD-associated hepatic fibrogenesis. Life Sci. 2021;264:118619.
155. Nevzorova YA, Bangen JM, Hu W, et al. Cyclin E1 controls proliferation of hepatic stellate cells and is essential for liver fibrogenesis in mice. Hepatology. 2012;56:1140-9.
156. Chiangjong W, Netsirisawan P, Hongeng S, Chutipongtanate S. Red blood cell extracellular vesicle-based drug delivery: challenges and opportunities. Front Med. 2021;8:761362.
157. Rodríguez DA, Vader P. Extracellular vesicle-based hybrid systems for advanced drug delivery. Pharmaceutics. 2022;14:267.
158. Piffoux M, Silva AKA, Wilhelm C, Gazeau F, Tareste D. Modification of extracellular vesicles by fusion with liposomes for the design of personalized biogenic drug delivery systems. ACS Nano. 2018;12:6830-42.
159. der Koog L, Gandek TB, Nagelkerke A. Liposomes and extracellular vesicles as drug delivery systems: a comparison of composition, pharmacokinetics, and functionalization. Adv Healthc Mater. 2022;11:e2100639.
160. Zhang YW, Hou LS, Xing JH, Zhang TR, Zhou SY, Zhang BL. Two-membrane hybrid nanobiomimetic delivery system for targeted autophagy inhibition of activated hepatic stellate cells to synergistically treat liver fibrosis. ACS Appl Mater Interfaces. ;2023:50863-77.
161. Ji K, Fan M, Huang D, et al. Clodronate-nintedanib-loaded exosome-liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity. Biomater Sci. 2022;10:702-13.
