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REVIEW

Mesenchymal Stem Cell–Derived Exosomes in Various Chronic Liver Diseases: Hype or Hope?

, , , , , , , & show all
Pages 171-189 | Received 12 Sep 2023, Accepted 27 Dec 2023, Published online: 10 Jan 2024

References

  • Wu Y, Min J, Ge C, et al. Interleukin 22 in Liver Injury, Inflammation and Cancer. Int J Biol Sci. 2020;16(13):2405–2413. doi:10.7150/ijbs.38925
  • Carmona C, Claxton L, O’Brien A, Hebditch V. Cirrhosis in over 16s: assessment and management-updated summary of NICE guidance. BMJ. 2023;383:2598. doi:10.1136/bmj.p2598
  • Sobeh M, Hamza MS, Ashour ML, et al. A polyphenol-rich fraction from Eugenia uniflora exhibits antioxidant and hepatoprotective activities in vivo. Pharmaceuticals. 2020;13(5):84.
  • Comarmond C, Cacoub P, Saadoun D. Treatment of chronic hepatitis C-associated cryoglobulinemia vasculitis at the era of direct-acting antivirals. Therap Adv Gastroenterol. 2020;13:1756284820942617. doi:10.1177/1756284820942617
  • Udompap P, Kim D, Kim WR. Current and Future Burden of Chronic Nonmalignant Liver Disease. Clin Gastroenterol Hepatol. 2015;13(12):2031–2041. doi:10.1016/j.cgh.2015.08.015
  • Starkey Lewis P, Campana L, Aleksieva N, et al. Alternatively activated macrophages promote resolution of necrosis following acute liver injury. J Hepatol. 2020;73(2):349–360. doi:10.1016/j.jhep.2020.02.031
  • Caldez MJ, Bjorklund M, Kaldis P. Cell cycle regulation in NAFLD: when imbalanced metabolism limits cell division. Hepatol Int. 2020;14(4):463–474. doi:10.1007/s12072-020-10066-6
  • Minami T, Aoyagi K, Kawahara A, et al. Evaluation of the expression of bone marrow-derived mesenchymal stem cells and cancer-associated fibroblasts in the stroma of gastric cancer tissue. Ann Gastroenterol Surg. 2020;4(4):464–474. doi:10.1002/ags3.12347
  • Freedman BR, Mooney DJ. Biomaterials to Mimic and Heal Connective Tissues. Adv Mater. 2019;31(19):e1806695. doi:10.1002/adma.201806695
  • Gomzikova MO, Aimaletdinov AM, Bondar OV, et al. Immunosuppressive properties of cytochalasin B-induced membrane vesicles of mesenchymal stem cells: comparing with extracellular vesicles derived from mesenchymal stem cells. Sci Rep. 2020;10(1):10740. doi:10.1038/s41598-020-67563-9
  • Li Q, Chen X, Li J. Marrow-derived mesenchymal stem cells regulate the inflammatory response and repair alveolar type II epithelial cells in acute lung injury of rats. J Int Med Res. 2020;48(4):300060520909027. doi:10.1177/0300060520909027
  • Li Z, Gong X, Li D, Yang X, Shi Q, Ju X. Intratracheal Transplantation of Amnion-Derived Mesenchymal Stem Cells Ameliorates Hyperoxia-Induced Neonatal Hyperoxic Lung Injury via Aminoacyl-Peptide Hydrolase. Int J Stem Cells. 2020;13(2):221–236. doi:10.15283/ijsc19110
  • Ni Z, Zhou S, Li S, et al. Exosomes: roles and therapeutic potential in osteoarthritis. Bone Res. 2020;8:25. doi:10.1038/s41413-020-0100-9
  • Solis MA, I M, Correa R, Huang LLH. Stem cells as a potential therapy for diabetes mellitus: a call-to-action in Latin America. Diabetol Metab Syndr. 2019;11:20. doi:10.1186/s13098-019-0415-0
  • Takayama Y, Kusamori K, Katsurada Y, Obana S, Itakura S, Nishikawa M. Efficient delivery of mesenchymal stem/stromal cells to injured liver by surface PEGylation. Stem Cell Res Ther. 2023;14(1):216. doi:10.1186/s13287-023-03446-w
  • Karaahmet F, Kocaman SA. Endothelial progenitor cells and mesenchymal stem cells to overcome vascular deterioration and cytokine storm in critical patients with COVID-19. Med Hypotheses. 2020;144:109973. doi:10.1016/j.mehy.2020.109973
  • Seyedrazizadeh S-Z, Poosti S, Nazari A, et al. Extracellular vesicles derived from human ES-MSCs protect retinal ganglion cells and preserve retinal function in a rodent model of optic nerve injury. Stem Cell Res Ther. 2020;11(1):203. doi:10.1186/s13287-020-01702-x
  • Xu B, Yuan F-Z, Lin L, et al. The Higher Inherent Therapeutic Potential of Biomaterial-Based hDPSCs and hEnSCs for Pancreas Diseases. Front Bioeng Biotechnol. 2020;8:636. doi:10.3389/fbioe.2020.00636
  • Wang J, Fu X, Yan Y, et al. In vitro differentiation of rhesus macaque bone marrow- and adipose tissue-derived MSCs into hepatocyte-like cells. Exp Ther Med. 2020;20(1):251–260. doi:10.3892/etm.2020.8676
  • Mishra VK, Shih -H-H, Parveen F, et al. Identifying the Therapeutic Significance of Mesenchymal Stem Cells. Cells. 2020;9(5):1145.
  • Fan T, Qu R, Yu Q, et al. Bioinformatics analysis of the biological changes involved in the osteogenic differentiation of human mesenchymal stem cells. J Cell Mol Med. 2020;24(14):7968–7978. doi:10.1111/jcmm.15429
  • Allameh A, Ahmadi-Ashtiani HR, Maleki N. Glutathione-related inflammatory signature in hepatocytes differentiated from the progenitor mesenchymal stem cells. Heliyon. 2020;6(6):e04149. doi:10.1016/j.heliyon.2020.e04149
  • Yao Z, Liu H, Yang M, et al. Bone marrow mesenchymal stem cell-derived endothelial cells increase capillary density and accelerate angiogenesis in mouse hindlimb ischemia model. Stem Cell Res Ther. 2020;11(1):221. doi:10.1186/s13287-020-01710-x
  • Balbi C, Costa A, Barile L, Bollini S. Message in a Bottle: upgrading Cardiac Repair into Rejuvenation. Cells. 2020;9(3):548.
  • Zhang J, Xie B, Hashimoto K. Current status of potential therapeutic candidates for the COVID-19 crisis. Brain Behav Immun. 2020;87:59–73. doi:10.1016/j.bbi.2020.04.046
  • Krambs JR, Abou Ezzi G, Yao J-C, Link DC. Canonical signaling by TGF family members in mesenchymal stromal cells is dispensable for hematopoietic niche maintenance under basal and stress conditions. PLoS One. 2020;15(5):e0233751. doi:10.1371/journal.pone.0233751
  • Wang L, Zhang L, Liang X, et al. Adipose Tissue-Derived Stem Cells from Type 2 Diabetics Reveal Conservative Alterations in Multidimensional Characteristics. Int J Stem Cells. 2020;13(2):268–278. doi:10.15283/ijsc20028
  • Chen J, Li M, Liu A-Q, et al. Gli1+ Cells Couple with Type H Vessels and Are Required for Type H Vessel Formation. Stem Cell Reports. 2020;15(1):110–124. doi:10.1016/j.stemcr.2020.06.007
  • Parhizkar Roudsari P, Alavi-Moghadam S, Payab M, et al. Auxiliary role of mesenchymal stem cells as regenerative medicine soldiers to attenuate inflammatory processes of severe acute respiratory infections caused by COVID-19. Cell Tissue Bank. 2020;21(3):405–425. doi:10.1007/s10561-020-09842-3
  • Basiri A, Pazhouhnia Z, Beheshtizadeh N, Hoseinpour M, Saghazadeh A, Rezaei N. Regenerative Medicine in COVID-19 Treatment: real Opportunities and Range of Promises. Stem Cell Rev Rep. 2021;17(1):163–175. doi:10.1007/s12015-020-09994-5
  • Yu C, Peall IW, Pham SH, Okolicsanyi RK, Griffiths LR, Haupt LM. Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance. Int J Mol Sci. 2020;21(11):145.
  • Carvalheiro T, Zimmermann M, Radstake TRDJ, Marut W. Novel insights into dendritic cells in the pathogenesis of systemic sclerosis. Clin Exp Immunol. 2020;201(1):25–33. doi:10.1111/cei.13417
  • Fan D, Zeng M, Xia Q, et al. Efficacy and safety of umbilical cord mesenchymal stem cells in treatment of cesarean section skin scars: a randomized clinical trial. Stem Cell Res Ther. 2020;11(1):244. doi:10.1186/s13287-020-01695-7
  • van Best N, Rolle-Kampczyk U, Schaap FG, et al. Bile acids drive the newborn’s gut microbiota maturation. Nat Commun. 2020;11(1):3692. doi:10.1038/s41467-020-17183-8
  • Alqahtani SA, Schattenberg M. Liver injury in COVID-19: the current evidence. United Eur Gastroenterol J. 2020;8(5):509–519. doi:10.1177/2050640620924157
  • Furuta T, Furuya K, Zheng Y-W, Oda T. Novel alternative transplantation therapy for orthotopic liver transplantation in liver failure: a systematic review. World J Transplant. 2020;10(3):64–78. doi:10.5500/wjt.v10.i3.64
  • Petryk N, Shevchenko O. Mesenchymal Stem Cells Anti-Inflammatory Activity in Rats: proinflammatory Cytokines. J Inflamm Res. 2020;13:293–301. doi:10.2147/JIR.S256932
  • Lotfi M, Hamblin MR, Rezaei N. COVID-19: transmission, prevention, and potential therapeutic opportunities. Clin Chim Acta. 2020;508:254–266. doi:10.1016/j.cca.2020.05.044
  • Ullah M, Liu DD, Rai S, et al. Reversing Acute Kidney Injury Using Pulsed Focused Ultrasound and MSC Therapy: a Role for HSP-Mediated PI3K/AKT Signaling. Mol Ther Methods Clin Dev. 2020;17:683–694. doi:10.1016/j.omtm.2020.03.023
  • Cai J, Wu J, Wang J, et al. Extracellular vesicles derived from different sources of mesenchymal stem cells: therapeutic effects and translational potential. Cell Biosci. 2020;10:69. doi:10.1186/s13578-020-00427-x
  • Ikeda T, Nishita M, Hoshi K, Honda T, Kakeji Y, Minami Y. Mesenchymal stem cell-derived CXCL16 promotes progression of gastric cancer cells by STAT3-mediated expression of Ror1. Cancer Sci. 2020;111(4):1254–1265. doi:10.1111/cas.14339
  • 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;14:252–261. doi:10.1016/j.reth.2020.03.012
  • Arnold P, Li W, et al. Joint Reconstituted Signaling of the IL-6 Receptor via Extracellular Vesicles. Cells. 2020;9(5):1307.
  • Krammer TL, Mayr M, Hackl M. microRNAs as promising biomarkers of platelet activity in antiplatelet therapy monitoring. Int J Mol Sci. 2020;21:254.
  • Shimizu A, Sawada K, Kimura T. Pathophysiological Role and Potential Therapeutic Exploitation of Exosomes in Ovarian Cancer. Cells. 2020;9(4):814.
  • Campos A, Leyton L, Quest AFG. Caveolin-1 function at the plasma membrane and in intracellular compartments in cancer. Cancer Metastasis Rev. 2020;39(2):435–453. doi:10.1007/s10555-020-09890-x
  • Seo Y, Kim H-S, Hong I-S. Stem Cell-Derived Extracellular Vesicles as Immunomodulatory Therapeutics. Stem Cells Int. 2019;2019:5126156. doi:10.1155/2019/5126156
  • Tsiapalis D, O’Driscoll L. Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications. Cells. 2020;9(4):991.
  • Ryu J-S, Seo SY, Jeong E-J, et al. Ganglioside GM3 Up-Regulate Chondrogenic Differentiation by Transform Growth Factor Receptors. Int J Mol Sci. 2020;21(6):548.
  • Lee DB, Verstraete FJM, Arzi B. An Update on Feline Chronic Gingivostomatitis. Vet Clin North Am Small Anim Pract. 2020;50(5):973–982. doi:10.1016/j.cvsm.2020.04.002
  • Volleman TNE, Schol J, Morita K, Sakai D, Watanabe M. Wnt3a and wnt5a as Potential Chondrogenic Stimulators for Nucleus Pulposus Cell Induction: a Comprehensive Review. Neurospine. 2020;17(1):19–35. doi:10.14245/ns.2040040.020
  • Hutchings G, Janowicz K, Moncrieff L, et al. The Proliferation and Differentiation of Adipose-Derived Stem Cells in Neovascularization and Angiogenesis. Int J Mol Sci. 2020;21(11):991.
  • Bao X, Wang J, Zhou G, et al. Extended in vitro culture of primary human mesenchymal stem cells downregulates Brca1-related genes and impairs DNA double-strand break recognition. FEBS Open Bio. 2020;10(7):1238–1250. doi:10.1002/2211-5463.12867
  • Shi R, Lian W, Jin Y, et al. Role and effect of vein-transplanted human umbilical cord mesenchymal stem cells in the repair of diabetic foot ulcers in rats. Acta Biochim Biophys Sin (Shanghai). 2020;52(6):620–630. doi:10.1093/abbs/gmaa039
  • Gnecchi M, He H, Liang OD, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005;11(4):367–368.
  • Gnecchi M, He H, Noiseux N, et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 2006;20(6):661–669.
  • Okazaki T, Magaki T, Takeda M, et al. Intravenous administration of bone marrow stromal cells increases survivin and Bcl-2 protein expression and improves sensorimotor function following ischemia in rats. Neurosci Lett. 2008;430(2):109–114.
  • Wang S-P, Wang Z-H, Peng D-Y, S-M L, Wang H, Wang X-H. Therapeutic effect of mesenchymal stem cells in rats with intracerebral hemorrhage: reduced apoptosis and enhanced neuroprotection. Mol Med Rep. 2012;6(4):848–854. doi:10.3892/mmr.2012.997
  • Wei H, Li F, Xue T, et al. MicroRNA-122-functionalized DNA tetrahedron stimulate hepatic differentiation of human mesenchymal stem cells for acute liver failure therapy. Bioact Mater. 2023;28:50–60. doi:10.1016/j.bioactmat.2023.04.024
  • Hu C, Li L. In vitro culture of isolated primary hepatocytes and stem cell-derived hepatocyte-like cells for liver regeneration. Protein Cell. 2015;6(8):562–574. doi:10.1007/s13238-015-0180-2
  • Z-H L, Wang Y-L, Wang H-J, J-H W, Tan Y-Z. Rapamycin-Preactivated Autophagy Enhances Survival and Differentiation of Mesenchymal Stem Cells After Transplantation into Infarcted Myocardium. Stem Cell Rev Rep. 2020;16(2):344–356. doi:10.1007/s12015-020-09952-1
  • Zhang Y, Li Y, Li W, et al. Therapeutic Effect of Human Umbilical Cord Mesenchymal Stem Cells at Various Passages on Acute Liver Failure in Rats. Stem Cells Int. 2018;2018:7159465. doi:10.1155/2018/7159465
  • Zhou X, Jin N, Wang F, Chen B. Mesenchymal stem cells: a promising way in therapies of graft-versus-host disease. Cancer Cell Int. 2020;20:114. doi:10.1186/s12935-020-01193-z
  • Buono L, Scalabrin S, De Iuliis M, et al. Mesenchymal Stem Cell-Derived Extracellular Vesicles Protect Human Corneal Endothelial Cells from Endoplasmic Reticulum Stress-Mediated Apoptosis. Int J Mol Sci. 2021;22(9):4930.
  • Moayedfard Z, Sani F, Alizadeh A, Bagheri Lankarani K, Zarei M, Azarpira N. The role of the immune system in the pathogenesis of NAFLD and potential therapeutic impacts of mesenchymal stem cell-derived extracellular vesicles. Stem Cell Res Ther. 2022;13(1):242. doi:10.1186/s13287-022-02929-6
  • Khatri M, Richardson LA, Meulia T. Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model. Stem Cell Res Ther. 2018;9(1):17. doi:10.1186/s13287-018-0774-8
  • Wu R, Fan X, Wang Y, et al. Mesenchymal Stem Cell-Derived Extracellular Vesicles in Liver Immunity and Therapy. Front Immunol. 2022;13:833878. doi:10.3389/fimmu.2022.833878
  • Zhao M, Liu S, Wang C, et al. Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Mitochondrial Damage and Inflammation by Stabilizing Mitochondrial DNA. ACS Nano. 2021;15(1):1519–1538. doi:10.1021/acsnano.0c08947
  • Branscome H, Paul S, Yin D, et al. Use of Stem Cell Extracellular Vesicles as a “Holistic” Approach to CNS Repair. Front Cell Dev Biol. 2020;8:455. doi:10.3389/fcell.2020.00455
  • Yin L, Liu X, Shi Y, et al. Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine. Cells. 2020;9(3):548.
  • Li Q, Huang Z, Wang Q, et al. Targeted immunomodulation therapy for cardiac repair by platelet membrane engineering extracellular vesicles via hitching peripheral monocytes. Biomaterials. 2022;284:121529. doi:10.1016/j.biomaterials.2022.121529
  • Aneesh A, Liu A, Moss HE, et al. Emerging concepts in the treatment of optic neuritis: mesenchymal stem cell-derived extracellular vesicles. Stem Cell Res Ther. 2021;12(1):594. doi:10.1186/s13287-021-02645-7
  • Fujii S, Miura Y. Immunomodulatory and Regenerative Effects of MSC-Derived Extracellular Vesicles to Treat Acute GVHD. Stem Cells. 2022;40(11):977–990. doi:10.1093/stmcls/sxac057
  • Harrell CR, Jovicic N, Djonov V, Volarevic V. Therapeutic Use of Mesenchymal Stem Cell-Derived Exosomes: from Basic Science to Clinics. Pharmaceutics. 2020;12(5):991.
  • Qiu L, Wang J, Chen M, Chen F, Tu W. Exosomal microRNA‑146a derived from mesenchymal stem cells increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2‑mediated PI3K/Akt axis. Int J Mol Med. 2020;46(2):609–620. doi:10.3892/ijmm.2020.4634
  • Wang M, Yu F, Li P, Wang K. Emerging Function and Clinical Significance of Exosomal circRNAs in Cancer. Mol Ther Nucleic Acids. 2020;21:367–383. doi:10.1016/j.omtn.2020.06.008
  • Gao S, Zhu H, Zuo X, Luo H. Cathepsin G and Its Role in Inflammation and Autoimmune Diseases. Arch Rheumatol. 2018;33(4):498–504. doi:10.5606/ArchRheumatol.2018.6595
  • Lu T, Zhang J, Cai J, et al. Extracellular vesicles derived from mesenchymal stromal cells as nanotherapeutics for liver ischaemia-reperfusion injury by transferring mitochondria to modulate the formation of neutrophil extracellular traps. Biomaterials. 2022;284:121486. doi:10.1016/j.biomaterials.2022.121486
  • Pan L-F, Niu Z-Q, Ren S, et al. Could extracellular vesicles derived from mesenchymal stem cells be a potential therapy for acute pancreatitis-induced cardiac injury? World J Stem Cells. 2023;15(7):654–664. doi:10.4252/wjsc.v15.i7.654
  • Qian X, An N, Ren Y, Yang C, Zhang X, Li L. Immunosuppressive Effects of Mesenchymal Stem Cells-derived Exosomes. Stem Cell Rev Rep. 2021;17(2):411–427. doi:10.1007/s12015-020-10040-7
  • Cha K-Y, Cho W, Park S, et al. Generation of bioactive MSC-EVs for bone tissue regeneration by tauroursodeoxycholic acid treatment. J Control Release. 2023;354:45–56. doi:10.1016/j.jconrel.2022.12.053
  • Pu Q, Xiu G, Sun J, Liu P, Ling B. Progress on the effect of mesenchymal stem cell derived exosomes on multiple organ dysfunction in sepsis. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021;33(6):757–760. doi:10.3760/cma.j.cn121430-20200908-00620
  • Wang J-H, Liu X-L, Sun J-M, Yang J-H, D-H X, Yan -S-S. Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: a systematic review. World J Stem Cells. 2020;12(8):879–896. doi:10.4252/wjsc.v12.i8.879
  • Gupta S, Pinky V, et al. Comparative Evaluation of Anti-Fibrotic Effect of Tissue Specific Mesenchymal Stem Cells Derived Extracellular Vesicles for the Amelioration of CCl4 Induced Chronic Liver Injury. Stem Cell Rev Rep. 2022;18(3):1097–1112. doi:10.1007/s12015-021-10313-9
  • Angioni R, Liboni C, Herkenne S, et al. CD73+ extracellular vesicles inhibit angiogenesis through adenosine A2B receptor signalling. J Extracell Vesicles. 2020;9(1):1757900. doi:10.1080/20013078.2020.1757900
  • Xin D, Li T, Chu X, Ke H, Liu D, Wang Z. MSCs-extracellular vesicles attenuated neuroinflammation, synapse damage and microglial phagocytosis after hypoxia-ischemia injury by preventing osteopontin expression. Pharmacol Res. 2021;164:105322. doi:10.1016/j.phrs.2020.105322
  • Pu Y, Li C, Qi X, et al. Extracellular Vesicles from NMN Preconditioned Mesenchymal Stem Cells Ameliorated Myocardial Infarction via miR-210-3p Promoted Angiogenesis. Stem Cell Rev Rep. 2023;19(4):1051–1066. doi:10.1007/s12015-022-10499-6
  • Wu Y, Peng W, Fang M, Wu M, Wu M. MSCs-Derived Extracellular Vesicles Carrying miR-212-5p Alleviate Myocardial Infarction-Induced Cardiac Fibrosis via NLRC5/VEGF/TGF-β1/SMAD Axis. J Cardiovasc Transl Res. 2022;15(2):302–316. doi:10.1007/s12265-021-10156-2
  • Han M, Cao Y, Xue H, et al. Neuroprotective Effect of Mesenchymal Stromal Cell-Derived Extracellular Vesicles Against Cerebral Ischemia-Reperfusion-Induced Neural Functional Injury: a Pivotal Role for AMPK and JAK2/STAT3/NF-ΰB Signaling Pathway Modulation. Drug Des Devel Ther. 2020;14:2865–2876. doi:10.2147/DDDT.S248892
  • Gholami L, Nooshabadi VT, Shahabi S, et al. Extracellular vesicles in bone and periodontal regeneration: current and potential therapeutic applications. Cell Biosci. 2021;11(1):16. doi:10.1186/s13578-020-00527-8
  • Rezaie J, Nejati V, Mahmoodi M, Ahmadi M. Mesenchymal stem cells derived extracellular vesicles: a promising nanomedicine for drug delivery system. Biochem Pharmacol. 2022;203:115167. doi:10.1016/j.bcp.2022.115167
  • Gentile P, Sterodimas A. Adipose Stem Cells (ASCs) and Stromal Vascular Fraction (SVF) as a Potential Therapy in Combating (COVID-19)-Disease. Aging Dis. 2020;11(3):465–469. doi:10.14336/AD.2020.0422
  • Abreu H, Canciani E, Raineri D, Cappellano G, Rimondini L, Chiocchetti A. Extracellular Vesicles in Musculoskeletal Regeneration: modulating the Therapy of the Future. Cells. 2021;11(1).
  • Liao Z, Liu C, Wang L, Sui C, Zhang H. Therapeutic Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Female Reproductive Diseases. Front Endocrinol (Lausanne). 2021;12:665645. doi:10.3389/fendo.2021.665645
  • Zhang J, Lu T, Xiao J, et al. MSC-derived extracellular vesicles as nanotherapeutics for promoting aged liver regeneration. J Control Release. 2023;356:402–415. doi:10.1016/j.jconrel.2023.02.032
  • Diniz AB, Antunes M, Lacerda V, et al. Imaging and immunometabolic phenotyping uncover changes in the hepatic immune response in the early phases of NAFLD. JHEP Rep. 2020;2(4):100117. doi:10.1016/j.jhepr.2020.100117
  • Kjã¦rgaard K, Sandahl TD, Frisch K, et al. Intravenous and oral copper kinetics, biodistribution and dosimetry in healthy humans studied by [64Cu]copper PET/CT. EJNMMI Radiopharm Chem. 2020;5(1):15. doi:10.1186/s41181-020-00100-1
  • Fahey S, Dempsey E, Long A. The role of chemokines in acute and chronic hepatitis C infection. Cell Mol Immunol. 2014;11(1):25–40. doi:10.1038/cmi.2013.37
  • Patel SR, Lundgren TS, Spencer HT, Doering CB. The Immune Response to the fVIII Gene Therapy in Preclinical Models. Front Immunol. 2020;11:494. doi:10.3389/fimmu.2020.00494
  • Gottwick C, Carambia A, Herkel J. Harnessing the liver to induce antigen-specific immune tolerance. Semin Immunopathol. 2022;44(4):475–484. doi:10.1007/s00281-022-00942-8
  • Lin L, Gong H, Li R, et al. Nanodrug with ROS and pH Dual-Sensitivity Ameliorates Liver Fibrosis via Multicellular Regulation. Adv Sci. 2020;7(7):1903138. doi:10.1002/advs.201903138
  • Horng J-H, Lin W-H, C-R W, et al. HBV X protein-based therapeutic vaccine accelerates viral antigen clearance by mobilizing monocyte infiltration into the liver in HBV carrier mice. J Biomed Sci. 2020;27(1):70. doi:10.1186/s12929-020-00662-x
  • Van Herck M, Vonghia L, Kwanten WJ, et al. Diet Reversal and Immune Modulation Show Key Role for Liver and Adipose Tissue T Cells in Murine Nonalcoholic Steatohepatitis. Cell Mol Gastroenterol Hepatol. 2020;10(3):467–490. doi:10.1016/j.jcmgh.2020.04.010
  • Asadipour M, Fazeli P, Zohouri M, et al. IL-18 in Blood Serum of Hepatitis C Patients Might be of Predictive Value for Individual Outcomes. Infect Disord Drug Targets. 2021;21(3):389–393. doi:10.2174/1871526520666200707113401
  • De Luca L, Trino S, Laurenzana I, et al. Mesenchymal Stem Cell Derived Extracellular Vesicles: a Role in Hematopoietic Transplantation? Int J Mol Sci. 2017;18(5):852.
  • Cai P, Mu Y, Olveda RM, Ross AG, Olveda DU, McManus DP. Serum Exosomal miRNAs for Grading Hepatic Fibrosis Due to Schistosomiasis. Int J Mol Sci. 2020;21:5548.
  • Morã¡n L, Cubero FJ. Extracellular vesicles in liver disease and beyond. World J Gastroenterol. 2018;24(40):4519–4526. doi:10.3748/wjg.v24.i40.4519
  • Chen L, F-B L, Chen D-Z, et al. BMSCs-derived miR-223-containing exosomes contribute to liver protection in experimental autoimmune hepatitis. Mol Immunol. 2018;93:38–46. doi:10.1016/j.molimm.2017.11.008
  • F-B L, Chen D-Z, Chen L, et al. Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p. Mol Cells. 2019;42(12):906–918. doi:10.14348/molcells.2019.2283
  • Tamura R, Uemoto S, Tabata Y. Immunosuppressive effect of mesenchymal stem cell-derived exosomes on a concanavalin A-induced liver injury model. Inflamm Regen. 2016;36:26. doi:10.1186/s41232-016-0030-5
  • Zhao J, Li Y, Jia R, Wang J, Shi M, Wang Y. Mesenchymal Stem Cells-Derived Exosomes as Dexamethasone Delivery Vehicles for Autoimmune Hepatitis Therapy. Front Bioeng Biotechnol. 2021;9:650376. doi:10.3389/fbioe.2021.650376
  • Chen L, Xiang B, Wang X, Xiang C. Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure. Stem Cell Res Ther. 2017;8(1):9. doi:10.1186/s13287-016-0453-6
  • Haga H, Yan IK, Takahashi K, Matsuda A, Patel T. Extracellular Vesicles from Bone Marrow-Derived Mesenchymal Stem Cells Improve Survival from Lethal Hepatic Failure in Mice. Stem Cells Transl Med. 2017;6(4):1262–1272. doi:10.1002/sctm.16-0226
  • Jiang L, Zhang S, Hu H, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acute liver failure by reducing the activity of the NLRP3 inflammasome in macrophages. Biochem Biophys Res Commun. 2019;508(3):735–741. doi:10.1016/j.bbrc.2018.11.189
  • Liu Y, Lou G, Li A, et al. AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages. EBioMedicine. 2018;36:140–150. doi:10.1016/j.ebiom.2018.08.054
  • Tan CY, Lai RC, Wong W, Dan YY, Lim S-K, Ho HK. Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther. 2014;5(3):76. doi:10.1186/scrt465
  • Zhang S, Jiang L, Hu H, et al. Pretreatment of exosomes derived from hUCMSCs with TNF-α ameliorates acute liver failure by inhibiting the activation of NLRP3 in macrophage. Life Sci. 2020;246:117401. doi:10.1016/j.lfs.2020.117401
  • Damania A, Jaiman D, Teotia AK, Kumar A. Mesenchymal stromal cell-derived exosome-rich fractionated secretome confers a hepatoprotective effect in liver injury. Stem Cell Res Ther. 2018;9(1):31. doi:10.1186/s13287-017-0752-6
  • Haga H, Yan IK, Borrelli DA, et al. Extracellular vesicles from bone marrow-derived mesenchymal stem cells protect against murine hepatic ischemia/reperfusion injury. Liver Transpl. 2017;23(6):791–803. doi:10.1002/lt.24770
  • Yao J, Zheng J, Cai J, et al. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response. FASEB J. 2019;33(2):1695–1710. doi:10.1096/fj.201800131RR
  • Zhang Y, Zhang X, Zhang H, et al. Mesenchymal Stem Cells Derived Extracellular Vesicles Alleviate Traumatic Hemorrhagic Shock Induced Hepatic Injury via IL-10/PTPN22-Mediated M2 Kupffer Cell Polarization. Front Immunol. 2021;12:811164. doi:10.3389/fimmu.2021.811164
  • Xie K, Liu L, Chen J, Liu F. Exosomes derived from human umbilical cord blood mesenchymal stem cells improve hepatic ischemia reperfusion injury via delivering miR-1246. Cell Cycle. 2019;18(24):3491–3501. doi:10.1080/15384101.2019.1689480
  • Zheng J, Lu T, Zhou C, et al. Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Protect Liver Ischemia/Reperfusion Injury by Reducing CD154 Expression on CD4+ T Cells via CCT2. Adv Sci. 2020;7(18):1903746. doi:10.1002/advs.201903746
  • Anger F, Camara M, Ellinger E, et al. Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Improve Liver Regeneration After Ischemia Reperfusion Injury in Mice. Stem Cells Dev. 2019;28(21):1451–1462. doi:10.1089/scd.2019.0085
  • Angioni R, Cal㬠B, Vigneswara V, et al. Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: preclinical Data in MDR2 Knockout Mice. Int J Mol Sci. 2020;21(22):8874.
  • 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;320:328–336. doi:10.1016/j.jconrel.2020.01.042
  • 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(4):1471–1486. doi:10.1016/j.ymthe.2020.12.025
  • 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(6):845–854. doi:10.1089/scd.2012.0395
  • Mardpour S, Ghanian MH, Sadeghi-Abandansari H, et al. Hydrogel-Mediated Sustained Systemic Delivery of Mesenchymal Stem Cell-Derived Extracellular Vesicles Improves Hepatic Regeneration in Chronic Liver Failure. ACS Appl Mater Interfaces. 2019;11(41):37421–37433. doi:10.1021/acsami.9b10126
  • 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. doi:10.1155/2018/3212643
  • 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(1):98. doi:10.1186/s13287-019-1204-2
  • 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(4):537–552. doi:10.1007/s13770-020-00267-3
  • 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(1):437. doi:10.1186/s12951-021-01138-2
  • 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;336:285–295. doi:10.1016/j.jconrel.2021.06.031
  • 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(2):701–715. doi:10.1111/jcmm.16119
  • Cheng L, Yu P, Li F, et al. Human umbilical cord-derived mesenchymal stem cell-exosomal miR-627-5p ameliorates non-alcoholic fatty liver disease by repressing FTO expression. Hum Cell. 2021;34(6):1697–1708. doi:10.1007/s13577-021-00593-1
  • Niu Q, Wang T, Wang Z, et al. Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver disease via delivering miR-223-3p. Adipocyte. 2022;11(1):572–587. doi:10.1080/21623945.2022.2098583
  • Engelmann C, Zhang IW. Mechanisms of immunity in acutely decompensated cirrhosis and acute-on-chronic liver failure. Liver Int. 2023. doi:10.1111/liv.15644
  • Yu Z, Li J, Ren Z, et al. Switching from Fatty Acid Oxidation to Glycolysis Improves the Outcome of Acute-On-Chronic Liver Failure. Adv Sci. 2020;7(7):1902996. doi:10.1002/advs.201902996
  • Cao P, Chen Q, Shi C, Wang L, Gong Z. Fusobacterium nucleatum promotes the development of acute liver failure by inhibiting the NAD+ salvage metabolic pathway. Gut Pathog. 2022;14(1):29. doi:10.1186/s13099-022-00503-2
  • Zhang S, Hou Y, Yang J, et al. Application of mesenchymal stem cell exosomes and their drug-loading systems in acute liver failure. J Cell Mol Med. 2020;24(13):7082–7093. doi:10.1111/jcmm.15290
  • Fang X, Gao F, Yao Q, et al. Pooled Analysis of Mesenchymal Stromal Cell-Derived Extracellular Vesicle Therapy for Liver Disease in Preclinical Models. J Pers Med. 2023;13(3):441.
  • Yan Y, Jiang W, Tan Y, et al. hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury. Mol Ther. 2017;25(2):465–479. doi:10.1016/j.ymthe.2016.11.019
  • Dong X, Feng X, Liu J, et al. Characteristics of Intestinal Microecology during Mesenchymal Stem Cell-Based Therapy for Mouse Acute Liver Injury. Stem Cells Int. 2019;2019:2403793. doi:10.1155/2019/2403793
  • Heeren J, Scheja L. Metabolic-associated fatty liver disease and lipoprotein metabolism. Mol Metab. 2021;50:101238. doi:10.1016/j.molmet.2021.101238
  • Zhang J-B. Therapeutic Effect of Prolyl Endopeptidase Inhibitor in High-fat Diet-induced Metabolic Dysfunction-associated Fatty Liver Disease. J Clin Transl Hepatol. 2023;11(5):1035–1049. doi:10.14218/JCTH.2022.00110
  • Gao Z, Zhang C, Peng F, et al. Hypoxic mesenchymal stem cell-derived extracellular vesicles ameliorate renal fibrosis after ischemia-reperfusion injure by restoring CPT1A mediated fatty acid oxidation. Stem Cell Res Ther. 2022;13(1):191. doi:10.1186/s13287-022-02861-9
  • Wei S, Li A, Zhang L, Du M. GROWTH AND DEVELOPMENT SYMPOSIUM: STEM AND PROGENITOR CELLS IN ANIMAL GROWTH: long noncoding RNAs in adipogenesis and adipose development of meat animals12. J Anim Sci. 2019;97(6):2644–2657. doi:10.1093/jas/skz114
  • Grange C, Tritta S, Tapparo M, et al. Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy. Sci Rep. 2019;9(1):4468. doi:10.1038/s41598-019-41100-9
  • Komori A. Recent updates on the management of autoimmune hepatitis. Clin Mol Hepatol. 2021;27(1):58–69. doi:10.3350/cmh.2020.0189
  • Covelli C, Sacchi D, Sarcognato S, et al. Pathology of autoimmune hepatitis. Pathologica. 2021;113(3):185–193. doi:10.32074/1591-951X-241
  • Chung Y, Rahim MN, Graham JJ, Zen Y, Heneghan MA. An update on the pharmacological management of autoimmune hepatitis. Expert Opin Pharmacother. 2021;22(11):1475–1488. doi:10.1080/14656566.2021.1895747
  • Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol. 2009;27:229–265. doi:10.1146/annurev.immunol.021908.132715
  • Vanaja SK, Rathinam VAK, Fitzgerald KA. Mechanisms of inflammasome activation: recent advances and novel insights. Trends Cell Biol. 2015;25(5):308–315. doi:10.1016/j.tcb.2014.12.009
  • Liu X, Mi X, Wang Z, et al. Ginsenoside Rg3 promotes regression from hepatic fibrosis through reducing inflammation-mediated autophagy signaling pathway. Cell Death Dis. 2020;11(6):454. doi:10.1038/s41419-020-2597-7
  • Joseph J. Serum Marker Panels for Predicting Liver Fibrosis - An Update. Clin Biochem Rev. 2020;41(2):67–73. doi:10.33176/AACB-20-00002
  • Ponziani FR, Nicoletti A, Gasbarrini A, Pompili M. Diagnostic and therapeutic potential of the gut microbiota in patients with early hepatocellular carcinoma. Ther Adv Med Oncol. 2019;11:1758835919848184. doi:10.1177/1758835919848184
  • Qiu B-F, Zhang G-Q. Effect of the transdifferentiation of BECs into myofibroblasts on the pathogenesis of secondary cholestatic hepatic fibrosis. Exp Ther Med. 2019;17(4):2769–2776. doi:10.3892/etm.2019.7234
  • 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(2):479–489. doi:10.1016/j.ymthe.2019.10.016
  • Zhou J, Lin Y, Kang X, Liu Z, Zhang W, Xu F. microRNA-186 in extracellular vesicles from bone marrow mesenchymal stem cells alleviates idiopathic pulmonary fibrosis via interaction with SOX4 and DKK1. Stem Cell Res Ther. 2021;12(1):96. doi:10.1186/s13287-020-02083-x
  • Wang B, Yao K, Huuskes BM, et al. Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis. Mol Ther. 2016;24(7):1290–1301. doi:10.1038/mt.2016.90
  • Wang S, Li L, Liu T, Jiang W, Hu X. miR-19a/19b-loaded exosomes in combination with mesenchymal stem cell transplantation in a preclinical model of myocardial infarction. Regener Med. 2020;15(6):1749–1759. doi:10.2217/rme-2019-0136
  • Guan Y, Yao W, Yi K, et al. Nanotheranostics for the Management of Hepatic Ischemia-Reperfusion Injury. Small. 2021;17(23):e2007727. doi:10.1002/smll.202007727
  • Lee HM, Kim T, Choi HJ, et al. Influence of intraoperative oxygen content on early postoperative graft dysfunction in living donor liver transplantation: a STROBE-compliant retrospective observational study. Medicine (Baltimore). 2020;99(21):e20339. doi:10.1097/MD.0000000000020339
  • Valdã©s S, Paredes SD, Garcã-A Carreras C, et al. S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats. Antioxidants (Basel). 2023;12(8)4930.
  • van der Vlist EJ, Stoorvogel W, Arkesteijn GJA, Wauben MHM. Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry. Nat Protoc. 2012;7(7):1311–1326. doi:10.1038/nprot.2012.065
  • Pospichalova V, Svoboda J, Dave Z, et al. Simplified protocol for flow cytometry analysis of fluorescently labeled exosomes and microvesicles using dedicated flow cytometer. J Extracell Vesicles. 2015;4:25530. doi:10.3402/jev.v4.25530
  • Smith ZJ, Lee C, Rojalin T, et al. Single exosome study reveals subpopulations distributed among cell lines with variability related to membrane content. J Extracell Vesicles. 2015;4:28533. doi:10.3402/jev.v4.28533
  • Hoffman AS. Hydrogels for biomedical applications. Ann N Y Acad Sci. 2001;944:62–73.
  • Xu N, Xu J, Zheng X, Hui J. Preparation of Injectable Composite Hydrogels by Blending Poloxamers with Calcium Carbonate-Crosslinked Sodium Alginate. ChemistryOpen. 2020;9(4):451–458. doi:10.1002/open.202000040
  • Okusha Y, Eguchi T, Tran MT, et al. Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2/CTGF): CRISPR against Cancer. Cancers (Basel). 2020;12(4):548.
  • Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367:6478. doi:10.1126/science.aau6977
  • Li F, Zhang J, Yi K, et al. Delivery of Stem Cell Secretome for Therapeutic Applications. ACS Appl Bio Mater. 2022;5(5):2009–2030. doi:10.1021/acsabm.1c01312
  • 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(37):eabp9435. doi:10.1126/sciadv.abp9435