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ORIGINAL RESEARCH

BMP7-Loaded Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Ameliorate Liver Fibrosis by Targeting Activated Hepatic Stellate Cells

, , , , , & ORCID Icon show all
Pages 3475-3495 | Received 01 Dec 2023, Accepted 23 Mar 2024, Published online: 11 Apr 2024

References

  • Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115:209–218. doi:10.1172/JCI24282
  • Kardashian A, Serper M, Terrault N, et al. Health disparities in chronic liver disease. Hepatology. 2023;77:1382–1403. doi:10.1002/hep.32743
  • Puche JE, Saiman Y, Friedman SL. Hepatic stellate cells and liver fibrosis. Compr Physiol. 2013;3:1473–1492.
  • Trivedi P, Wang S, Friedman SL. The power of plasticity-metabolic regulation of hepatic stellate cells. Cell Metab. 2021;33:242–257. doi:10.1016/j.cmet.2020.10.026
  • Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol. 2021;18:151–166. doi:10.1038/s41575-020-00372-7
  • Parola M, Pinzani M. Liver fibrosis: pathophysiology, pathogenetic targets and clinical issues. Mol Aspects Med. 2019;65:37–55. doi:10.1016/j.mam.2018.09.002
  • Fu FU, Liu L, Halim H, Ju JU, Luo L, Song S. Mesenchymal stem cell migration and tissue repair. Cells. 2019;8(8):784. doi:10.3390/cells8080784
  • El Agha E, Kramann R, Schneider RK, et al. Mesenchymal stem cells in fibrotic disease. Cell Stem Cell. 2017;21(2):166–177. doi:10.1016/j.stem.2017.07.011
  • Tsuchiya A, Takeuchi S, Watanabe T, et al. Mesenchymal stem cell therapies for liver cirrhosis: mSCs as “conducting cells” for improvement of liver fibrosis and regeneration. Inflammation and Regeneration. 2019;39(1):18. doi:10.1186/s41232-019-0107-z
  • Yao Y, Xia Z, Cheng F, et al. Human placental mesenchymal stem cells ameliorate liver fibrosis in mice by upregulation of Caveolin 1 in hepatic stellate cells. Stem Cell Res Ther. 2021;12:294. doi:10.1186/s13287-021-02358-x
  • Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17:11–22. doi:10.1016/j.stem.2015.06.007
  • Li TT, Wang ZR, Yao WQ, Linghu EQ, Wang FS, Shi L. Stem cell therapies for chronic liver diseases: progress and challenges. Stem Cells Transl Med. 2022;11:900–911. doi:10.1093/stcltm/szac053
  • Yang X, Meng Y, Han Z, Ye F, Wei L, Zong C. Mesenchymal stem cell therapy for liver disease: full of chances and challenges. Cell Biosci. 2020;10:123. doi:10.1186/s13578-020-00480-6
  • Al-Azab M, Safi M, Idiiatullina E, Al-Shaebi F, Zaky MY. Aging of mesenchymal stem cell: machinery, markers, and strategies of fighting. Cell Mol Biol Lett. 2022;27:69. doi:10.1186/s11658-022-00366-0
  • Hwang NS, Zhang C, Hwang YS, Varghese S. Mesenchymal stem cell differentiation and roles in regenerative medicine. Wiley Interdiscip Rev Syst Biol Med. 2009;1:97–106. doi:10.1002/wsbm.26
  • Cheng W, Zeng Y, Wang D. Stem cell-based therapy for pulmonary fibrosis. Stem Cell Res Ther. 2022;13:492. doi:10.1186/s13287-022-03181-8
  • Liu P, Mao Y, Xie Y, Wei J, Yao J. Stem cells for treatment of liver fibrosis/cirrhosis: clinical progress and therapeutic potential. Stem Cell Res Ther. 2022;13:356. doi:10.1186/s13287-022-03041-5
  • Psaraki A, Ntari L, Karakostas C, Korrou-Karava D, Roubelakis MG. Extracellular vesicles derived from mesenchymal stem/stromal cells: the regenerative impact in liver diseases. Hepatology. 2022;75:1590–1603. doi:10.1002/hep.32129
  • Varderidou-Minasian S, Lorenowicz MJ. Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities. Theranostics. 2020;10:5979–5997. doi:10.7150/thno.40122
  • Cecchin R, Troyer Z, Witwer K, Morris K. Extracellular vesicles: the next generation in gene therapy delivery. Mol Ther. 2023;31:1225–1230. doi:10.1016/j.ymthe.2023.01.021
  • 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. doi:10.1186/s13287-020-01895-1
  • Lou G, Chen Z, Zheng M, Liu Y. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases. Exp Mol Med. 2017;49(e346):e346–e346. doi:10.1038/emm.2017.63
  • Ghafouri-Fard S, Niazi V, Hussen BM, Omrani MD, Taheri M, Basiri A. The emerging role of exosomes in the treatment of human disorders with a special focus on mesenchymal stem cells-derived exosomes. Front Cell Dev Biol. 2021;9:653296. doi:10.3389/fcell.2021.653296
  • Ceccotti E, Saccu G, Herrera Sanchez MB, Bruno S. Naïve or engineered extracellular vesicles from different cell sources: therapeutic tools for kidney diseases. Pharmaceutics. 2023;15(6):1715. doi:10.3390/pharmaceutics15061715
  • Hassanzadeh A, Rahman HS, Markov A, et al. Mesenchymal stem/stromal cell-derived exosomes in regenerative medicine and cancer; overview of development, challenges, and opportunities. Stem Cell Res Ther. 2021;12:297. doi:10.1186/s13287-021-02378-7
  • Fuloria S, Subramaniyan V, Dahiya R, et al. Mesenchymal stem cell-derived extracellular vesicles: regenerative potential and challenges. Biology (Basel). 2021;10:172. doi:10.3390/biology10030172
  • Wang X, Chen Y, Zhao Z, et al. Engineered exosomes with ischemic myocardium-targeting peptide for targeted therapy in myocardial infarction. J Am Heart Assoc. 2018;7:e008737. doi:10.1161/JAHA.118.008737
  • Lin Y, Yan M, Bai Z, et al. Huc-MSC-derived exosomes modified with the targeting peptide of aHSCs for liver fibrosis therapy. J Nanobiotechnology. 2022;20:432. doi:10.1186/s12951-022-01636-x
  • 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
  • Lu X, Guo H, Wei X, et al. Current status and prospect of delivery vehicle based on mesenchymal stem cell-derived exosomes in liver diseases. Int J Nanomed. 2023;18:2873–2890. doi:10.2147/IJN.S404925
  • Herrmann IK, Wood MJA, Fuhrmann G. Extracellular vesicles as a next-generation drug delivery platform. Nat Nanotechnol. 2021;16:748–759. doi:10.1038/s41565-021-00931-2
  • Zeisberg M, Hanai J, Sugimoto H, et al. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med. 2003;9:964–968. doi:10.1038/nm888
  • Yao H, Ge T, Zhang Y, et al. BMP7 antagonizes proliferative vitreoretinopathy through retinal pigment epithelial fibrosis in vivo and in vitro. FASEB J. 2019;33:3212–3224. doi:10.1096/fj.201800858RR
  • Weiskirchen R, Meurer SK, Gressner OA, Herrmann J, Borkham-Kamphorst E, Gressner AM. BMP-7 as antagonist of organ fibrosis. Front Biosci. 2009;14:4992–5012. doi:10.2741/3583
  • Zou GL, Zuo S, Lu S, et al. Bone morphogenetic protein-7 represses hepatic stellate cell activation and liver fibrosis via regulation of TGF-β/Smad signaling pathway. World J Gastroenterol. 2019;25:4222–4234. doi:10.3748/wjg.v25.i30.4222
  • Chen L, Zhou Q, Liu E, et al. rSjp40 inhibits activated hepatic stellate cells by promoting nuclear translocation of YB1 and inducing BMP-7/Smad1/5/8 pathway. Parasit Vectors. 2019;12:279. doi:10.1186/s13071-019-3539-z
  • Ji F, Wang K, Zhang Y, et al. MiR-542-3p controls hepatic stellate cell activation and fibrosis via targeting BMP-7. J Cell Biochem. 2019;120:4573–4581. doi:10.1002/jcb.27746
  • Mushahary D, Spittler A, Kasper C, Weber V, Charwat V. Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A. 2018;93:19–31. doi:10.1002/cyto.a.23242
  • Visan KS, Lobb RJ, Ham S, et al. Comparative analysis of tangential flow filtration and ultracentrifugation, both combined with subsequent size exclusion chromatography, for the isolation of small extracellular vesicles. J Extracell Vesicles. 2022;11:e12266.
  • Wang SS, Tang XT, Lin M, et al. Perivenous stellate cells are the main source of myofibroblasts and cancer-associated fibroblasts formed after chronic liver injuries. Hepatology. 2021;74:1578–1594. doi:10.1002/hep.31848
  • Schuppan D, Ashfaq-Khan M, Yang AT, Kim YO. Liver fibrosis: direct antifibrotic agents and targeted therapies. Matrix Biol. 2018;68–69:435–451. doi:10.1016/j.matbio.2018.04.006
  • Wang L, Bai G, Chen F. Human bone marrow mesenchymal stem cells suppress the proliferation of hepatic stellate cells by inhibiting the ubiquitination of p27. Biochem Cell Biol. 2017;95:628–633. doi:10.1139/bcb-2017-0127
  • 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;25:701–715. doi:10.1111/jcmm.16119
  • 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;29:1471–1486. doi:10.1016/j.ymthe.2020.12.025
  • Zhang WS, Zhang R, Ge Y, et al. S100a16 deficiency prevents hepatic stellate cells activation and liver fibrosis via inhibiting CXCR4 expression. Metabolism. 2022;135:155271. doi:10.1016/j.metabol.2022.155271
  • Meng D, Li Z, Wang G, Ling L, Wu Y, Zhang C. Carvedilol attenuates liver fibrosis by suppressing autophagy and promoting apoptosis in hepatic stellate cells. Biomed Pharmacother. 2018;108:1617–1627. doi:10.1016/j.biopha.2018.10.005
  • Zhang M, Serna-Salas S, Damba T, Borghesan M, Demaria M, Moshage H. Hepatic stellate cell senescence in liver fibrosis: characteristics, mechanisms and perspectives. Mech Ageing Dev. 2021;199:111572. doi:10.1016/j.mad.2021.111572
  • Kendall TJ, Hennedige S, Aucott RL, et al. p75 neurotrophin receptor signaling regulates hepatic myofibroblast proliferation and apoptosis in recovery from rodent liver fibrosis. Hepatology. 2009;49:901–910. doi:10.1002/hep.22701
  • Bruck R, Schey R, Aeed H, Hochman A, Genina O, Pines M. A protective effect of pyrrolidine dithiocarbamate in a rat model of liver cirrhosis. Liver Int. 2004;24:169–176. doi:10.1111/j.1478-3231.2004.00900.x
  • Li R, Li Z, Feng Y, et al. PDGFRβ-targeted TRAIL specifically induces apoptosis of activated hepatic stellate cells and ameliorates liver fibrosis. Apoptosis. 2020;25(1–2):105–119. doi:10.1007/s10495-019-01583-3
  • Arroyo N, Villamayor L, Díaz I, et al. GATA4 induces liver fibrosis regression by deactivating hepatic stellate cells. JCI Insight. 2021;6(23):e150059. doi:10.1172/jci.insight150059
  • Liu J, Kong D, Qiu J, et al. Praziquantel ameliorates CCl(4)-induced liver fibrosis in mice by inhibiting TGF-β/Smad signalling via up-regulating Smad7 in hepatic stellate cells. Br J Pharmacol. 2019;176:4666–4680. doi:10.1111/bph.14831
  • Dat NQ, Thuy LTT, Hieu VN, et al. Hexa histidine-tagged recombinant human cytoglobin deactivates hepatic stellate cells and inhibits liver fibrosis by scavenging reactive oxygen species. Hepatology. 2021;73:2527–2545.