Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Research Article

Fucoxanthin Enhances the Antifibrotic Potential of Placenta-derived Mesenchymal Stem Cells in a CCl4-induced Mouse Model of Liver

Author(s): Vasilii Slautin*, Konstantin Konyshev, Ilya Gavrilov, Olga Beresneva, Irina Maklakova and Dmitry Grebnev

Volume 19, Issue 11, 2024

Published on: 08 January, 2024

Page: [1484 - 1496] Pages: 13

DOI: 10.2174/011574888X279940231206100902

Price: $65

Abstract

Background: The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis.

Aim: This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis.

Methods: After PD-MSCs isolation and identification, outbred ICR/CD1 mice were divided into five groups: Control group, CCl4 group (CCl4), Fx group (CCl4+Fx), PD-MSCs group (CCl4+MSCs) and cotreatment group (CCl4+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+), matrix metalloproteinases (MMP-9+, MMP-13+), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas, and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β), hepatic growth factor (HGF), procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay.

Results: Compared to the single treatment with PD-MSCs or Fx, their combined administration significantly reduced liver enzyme activity, the severity of liver fibrosis, the proinflammatory cytokine levels, TGF-β level, α-SMA+, TIMP-1+ areas and the number of positive cells in them, and increased HGF level, MMP-13+, and MMP-9+ areas.

Conclusion: Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis, but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.

Keywords: Liver fibrosis, MSCs-based therapy, placenta-derived mesenchymal stem cells, fucoxanthin, hepatic stellate cells, TGF-β.

Graphical Abstract
[1]
Wang, J.; Chen, Z.; Sun, M.; Xu, H.; Gao, Y.; Liu, J.; Li, M. Characterization and therapeutic applications of mesenchymal stem cells for regenerative medicine. Tissue Cell, 2020, 64, 101330.
[http://dx.doi.org/10.1016/j.tice.2020.101330] [PMID: 32473704]
[2]
Cardinale, V.; Lanthier, N.; Baptista, P.M.; Carpino, G.; Carnevale, G.; Orlando, G.; Angelico, R.; Manzia, T.M.; Schuppan, D.; Pinzani, M.; Alvaro, D.; Ciccocioppo, R.; Uygun, B.E. Cell transplantation-based regenerative medicine in liver diseases. Stem Cell Reports, 2023, 18(8), 1555-1572.
[http://dx.doi.org/10.1016/j.stemcr.2023.06.005] [PMID: 37557073]
[3]
Mahjoor, M.; Fakouri, A.; Farokhi, S.; Nazari, H.; Afkhami, H.; Heidari, F. Regenerative potential of mesenchymal stromal cells in wound healing: unveiling the influence of normoxic and hypoxic environments. Front. Cell Dev. Biol., 2023, 11, 1245872.
[http://dx.doi.org/10.3389/fcell.2023.1245872] [PMID: 37900276]
[4]
Lou, S.; Duan, Y.; Nie, H.; Cui, X.; Du, J.; Yao, Y. Mesenchymal stem cells: Biological characteristics and application in disease therapy. Biochimie, 2021, 185, 9-21.
[http://dx.doi.org/10.1016/j.biochi.2021.03.003] [PMID: 33711361]
[5]
Liu, P.; Qian, Y.; Liu, X.; Zhu, X.; Zhang, X.; Lv, Y.; Xiang, J. Immunomodulatory role of mesenchymal stem cell therapy in liver fibrosis. Front. Immunol., 2023, 13, 1096402.
[http://dx.doi.org/10.3389/fimmu.2022.1096402] [PMID: 36685534]
[6]
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(1), 356.
[http://dx.doi.org/10.1186/s13287-022-03041-5] [PMID: 35883127]
[7]
Yao, L.; Hu, X.; Dai, K.; Yuan, M.; Liu, P.; Zhang, Q.; Jiang, Y. Mesenchymal stromal cells: Promising treatment for liver cirrhosis. Stem Cell Res. Ther., 2022, 13(1), 308.
[http://dx.doi.org/10.1186/s13287-022-03001-z] [PMID: 35841079]
[8]
Hu, X.; Ge, Q.; Zhang, Y.; Li, B.; Cheng, E.; Wang, Y.; Huang, Y. A review of the effect of exosomes from different cells on liver fibrosis. Biomed. Pharmacother., 2023, 161, 114415.
[http://dx.doi.org/10.1016/j.biopha.2023.114415] [PMID: 36812711]
[9]
Jones, B.; Li, C.; Park, M.S.; Lerch, A.; Jacob, V.; Johnson, N.; Kuang, J.Q.; Dhall, S.; Sathyamoorthy, M. Comprehensive comparison of amnion stromal cells and chorion stromal cells by RNA-seq. Int. J. Mol. Sci., 2021, 22(4), 1901.
[http://dx.doi.org/10.3390/ijms22041901] [PMID: 33672986]
[10]
Chen, L.; Merkhan, M.M.; Forsyth, N.R.; Wu, P. Chorionic and amniotic membrane-derived stem cells have distinct, and gestational diabetes mellitus independent, proliferative, differentiation, and immunomodulatory capacities. Stem Cell Res., 2019, 40, 101537.
[http://dx.doi.org/10.1016/j.scr.2019.101537] [PMID: 31422237]
[11]
Jeon, Y.J.; Kim, J.; Cho, J.H.; Chung, H.M.; Chae, J.I. Comparative analysis of human mesenchymal stem cells derived from bone marrow, placenta, and adipose tissue as sources of cell therapy. J. Cell. Biochem., 2016, 117(5), 1112-1125.
[http://dx.doi.org/10.1002/jcb.25395] [PMID: 26448537]
[12]
Zhang, Y.; Ravikumar, M.; Ling, L.; Nurcombe, V.; Cool, S.M. Age-related changes in the inflammatory status of human mesenchymal stem cells: implications for cell therapy. Stem Cell Reports, 2021, 16(4), 694-707.
[http://dx.doi.org/10.1016/j.stemcr.2021.01.021] [PMID: 33636113]
[13]
Gao, Y.; Chi, Y.; Chen, Y.; Wang, W.; Li, H.; Zheng, W.; Zhu, P.; An, J.; Duan, Y.; Sun, T.; Liu, X.; Xue, F.; Liu, W.; Fu, R.; Han, Z.; Zhang, Y.; Yang, R.; Cheng, T.; Wei, J.; Zhang, L.; Zhang, X. Multi-omics analysis of human mesenchymal stem cells shows cell aging that alters immunomodulatory activity through the downregulation of PD-L1. Nat. Commun., 2023, 14(1), 4373.
[http://dx.doi.org/10.1038/s41467-023-39958-5] [PMID: 37474525]
[14]
Torre, P.; Flores, A.I. Current status and future prospects of perinatal stem cells. Genes, 2020, 12(1), 6.
[http://dx.doi.org/10.3390/genes12010006] [PMID: 33374593]
[15]
Yao, Q.; Chen, W.; Yu, Y.; Gao, F.; Zhou, J.; Wu, J.; Pan, Q.; Yang, J.; Zhou, L.; Yu, J.; Cao, H.; Li, L. Human placental mesenchymal stem cells relieve primary sclerosing cholangitis via upregulation of TGR5 in Mdr2 −/− mice and human intrahepatic cholangiocyte organoid models. Research, 2023, 6, 0207.
[http://dx.doi.org/10.34133/research.0207] [PMID: 37600495]
[16]
Li, S.; Wang, J.; Jiang, B.; Jiang, J.; Luo, L.; Zheng, B.; Si, W. Mesenchymal stem cells derived from different perinatal tissues donated by same donors manifest variant performance on the acute liver failure model in mouse. Stem Cell Res. Ther., 2022, 13(1), 231.
[http://dx.doi.org/10.1186/s13287-022-02909-w] [PMID: 35659084]
[17]
Kim, S.H.; Kim, J.Y.; Park, S.Y.; Jeong, W.T.; Kim, J.M.; Bae, S.H.; Kim, G.J. Activation of the EGFR-PI3K- CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium. Stem Cell Res. Ther., 2021, 12(1), 551.
[http://dx.doi.org/10.1186/s13287-021-02616-y] [PMID: 34689832]
[18]
Na, J.; Song, J.; Kim, H.H.; Seok, J.; Kim, J.Y.; Jun, J.H.; Kim, G.J. Human placenta-derived mesenchymal stem cells trigger repair system in TAA-injured rat model via antioxidant effect. Aging, 2021, 13(1), 61-76.
[http://dx.doi.org/10.18632/aging.202348] [PMID: 33406506]
[19]
Yao, Y.; Xia, Z.; Cheng, F.; Jang, Q.; He, J.; Pan, C.; Zhang, L.; Ye, Y.; Wang, Y.; Chen, S.; Su, D.; Su, X.; Cheng, L.; Shi, G.; Dai, L.; Deng, H. Human placental mesenchymal stem cells ameliorate liver fibrosis in mice by upregulation of Caveolin1 in hepatic stellate cells. Stem Cell Res. Ther., 2021, 12(1), 294.
[http://dx.doi.org/10.1186/s13287-021-02358-x] [PMID: 34016164]
[20]
Slautin, V.N.; Grebnev, D.Y.; Maklakova, I.Y.; Sazonov, S.V. Fucoxanthin exert dose-dependent antifibrotic and anti-inflammatory effects on CCl4-induced liver fibrosis. J. Nat. Med., 2023, 77(4), 953-963.
[http://dx.doi.org/10.1007/s11418-023-01723-9] [PMID: 37391684]
[21]
Mumu, M.; Das, A.; Emran, T.B.; Mitra, S.; Islam, F.; Roy, A.; Karim, M.M.; Das, R.; Park, M.N.; Chandran, D.; Sharma, R.; Khandaker, M.U.; Idris, A.M.; Kim, B. Fucoxanthin: A promising phytochemical on diverse pharmacological targets. Front. Pharmacol., 2022, 13, 929442.
[http://dx.doi.org/10.3389/fphar.2022.929442] [PMID: 35983376]
[22]
Bae, M.; Kim, M.B.; Park, Y.K.; Lee, J.Y. Health benefits of fucoxanthin in the prevention of chronic diseases. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2020, 1865(11), 158618.
[http://dx.doi.org/10.1016/j.bbalip.2020.158618] [PMID: 31931174]
[23]
Li, N.; Gao, X.; Zheng, L.; Huang, Q.; Zeng, F.; Chen, H.; Farag, M.A.; Zhao, C. Advances in fucoxanthin chemistry and management of neurodegenerative diseases. Phytomedicine, 2022, 105, 154352.
[http://dx.doi.org/10.1016/j.phymed.2022.154352] [PMID: 35917771]
[24]
Miyashita, K.; Hosokawa, M. Fucoxanthin in the management of obesity and its related disorders. J. Funct. Foods, 2017, 36, 195-202.
[http://dx.doi.org/10.1016/j.jff.2017.07.009]
[25]
Winarto, J.; Song, D.G.; Pan, C.H. The role of fucoxanthin in non-alcoholic fatty liver disease. Int. J. Mol. Sci., 2023, 24(9), 8203.
[http://dx.doi.org/10.3390/ijms24098203] [PMID: 37175909]
[26]
Guan, B.; Chen, K.; Tong, Z.; Chen, L.; Chen, Q.; Su, J. Advances in fucoxanthin research for the prevention and treatment of inflammation-related diseases. Nutrients, 2022, 14(22), 4768.
[http://dx.doi.org/10.3390/nu14224768] [PMID: 36432455]
[27]
Liu, M.; Li, W.; Chen, Y.; Wan, X.; Wang, J. Fucoxanthin: A promising compound for human inflammation-related diseases. Life Sci., 2020, 255, 117850.
[http://dx.doi.org/10.1016/j.lfs.2020.117850] [PMID: 32470447]
[28]
Li, S.; Ren, X.; Wang, Y.; Hu, J.; Wu, H.; Song, S.; Yan, C. Fucoxanthin alleviates palmitate-induced inflammation in RAW 264.7 cells through improving lipid metabolism and attenuating mitochondrial dysfunction. Food Funct., 2020, 11(4), 3361-3370.
[http://dx.doi.org/10.1039/D0FO00442A] [PMID: 32232236]
[29]
Jeong, S.; Kim, M.B.; Baek, S.; Lee, J.; Lee, H.; Cao, B.; Kim, Y.; Cao, L.; Lee, S. Suppression of pro-inflammatory M1 polarization of LPS-stimulated RAW 264.7 macrophage cells by fucoxanthin-rich sargassum hemiphyllum. Mar. Drugs, 2023, 21(10), 533.
[http://dx.doi.org/10.3390/md21100533] [PMID: 37888467]
[30]
Ben Ammar, R.; Zahra, H.A.; Abu Zahra, A.M.; Alfwuaires, M.; Abdulaziz Alamer, S.; Metwally, A.M.; Althnaian, T.A.; Al-Ramadan, S.Y. Protective effect of fucoxanthin on zearalenone-induced hepatic damage through Nrf2 mediated by PI3K/AKT signaling. Mar. Drugs, 2023, 21(7), 391.
[http://dx.doi.org/10.3390/md21070391] [PMID: 37504922]
[31]
Kim, M.B.; Bae, M.; Hu, S.; Kang, H.; Park, Y.K.; Lee, J.Y. Fucoxanthin exerts anti-fibrogenic effects in hepatic stellate cells. Biochem. Biophys. Res. Commun., 2019, 513(3), 657-662.
[http://dx.doi.org/10.1016/j.bbrc.2019.04.052] [PMID: 30982574]
[32]
Li, Y.; Kim, M.B.; Park, Y.K.; Lee, J.Y. Fucoxanthin metabolites exert anti-fibrogenic and antioxidant effects in hepatic stellate cells. J. Agricult. Food Res., 2021, 6, 100245.
[http://dx.doi.org/10.1016/j.jafr.2021.100245]
[33]
Takatani, N.; Kono, Y.; Beppu, F.; Okamatsu-Ogura, Y.; Yamano, Y.; Miyashita, K.; Hosokawa, M. Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice. Biochem. Biophys. Res. Commun., 2020, 528(2), 305-310.
[http://dx.doi.org/10.1016/j.bbrc.2020.05.050] [PMID: 32475638]
[34]
Nan, Y.; Su, H.; Lian, X.; Wu, J.; Liu, S.; Chen, P.; Liu, S. Pathogenesis of liver fibrosis and its TCM therapeutic perspectives. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-12.
[http://dx.doi.org/10.1155/2022/5325431] [PMID: 35529927]
[35]
Zhang, C.Y.; Liu, S.; Yang, M. Treatment of liver fibrosis: Past, current, and future. World J. Hepatol., 2023, 15(6), 755-774.
[http://dx.doi.org/10.4254/wjh.v15.i6.755] [PMID: 37397931]
[36]
Liu, Y.B.; Chen, M.K. Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions. World J. Gastroenterol., 2022, 28(41), 5910-5930.
[http://dx.doi.org/10.3748/wjg.v28.i41.5910] [PMID: 36405106]
[37]
Zanetto, A.; Shalaby, S.; Gambato, M.; Germani, G.; Senzolo, M.; Bizzaro, D.; Russo, F.P.; Burra, P. New indications for liver transplantation. J. Clin. Med., 2021, 10(17), 3867.
[http://dx.doi.org/10.3390/jcm10173867] [PMID: 34501314]
[38]
Ngu, N.L.Y.; Flanagan, E.; Bell, S.; Le, S.T. Acute-on-chronic liver failure: Controversies and consensus. World J. Gastroenterol., 2023, 29(2), 232-240.
[http://dx.doi.org/10.3748/wjg.v29.i2.232] [PMID: 36687118]
[39]
Karvellas, C.J.; Francoz, C.; Weiss, E. Liver transplantation in acute-on-chronic liver failure. Transplantation, 2021, 105(7), 1471-1481.
[http://dx.doi.org/10.1097/TP.0000000000003550] [PMID: 33208692]
[40]
Huang, Q.; Yang, Y.; Luo, C.; Wen, Y.; Liu, R.; Li, S.; Chen, T.; Sun, H.; Tang, L. An efficient protocol to generate placental chorionic plate-derived mesenchymal stem cells with superior proliferative and immunomodulatory properties. Stem Cell Res. Ther., 2019, 10(1), 301.
[http://dx.doi.org/10.1186/s13287-019-1405-8] [PMID: 31623677]
[41]
Nallagangula, K.S.; Nagaraj, S.K.; Venkataswamy, L.; Chandrappa, M. Liver fibrosis: A compilation on the biomarkers status and their significance during disease progression. Future Sci. OA, 2018, 4(1), FSO250.
[http://dx.doi.org/10.4155/fsoa-2017-0083] [PMID: 29255622]
[42]
Sharma, P. Value of liver function tests in cirrhosis. J. Clin. Exp. Hepatol., 2022, 12(3), 948-964.
[http://dx.doi.org/10.1016/j.jceh.2021.11.004] [PMID: 35677506]
[43]
Ong, C.H.; Tham, C.L.; Harith, H.H.; Firdaus, N.; Israf, D.A. TGF-β-induced fibrosis: A review on the underlying mechanism and potential therapeutic strategies. Eur. J. Pharmacol., 2021, 911, 174510.
[http://dx.doi.org/10.1016/j.ejphar.2021.174510] [PMID: 34560077]
[44]
Gough, N.R.; Xiang, X.; Mishra, L. TGF-β signaling in liver, pancreas, and gastrointestinal diseases and cancer. Gastroenterology, 2021, 161(2), 434-452.e15.
[http://dx.doi.org/10.1053/j.gastro.2021.04.064] [PMID: 33940008]
[45]
Lee, Y-S.; Seki, E. In vivo and in vitro models to study liver fibrosis: Mechanisms and limitations. Cell Mol. Gastroenterol. Hepatol., 2023, 100788.
[http://dx.doi.org/10.1016/j.jcmgh.2023.05.010]
[46]
Wu, S.; Wang, X.; Xing, W.; Li, F.; Liang, M.; Li, K.; He, Y.; Wang, J. An update on animal models of liver fibrosis. Front. Med., 2023, 10, 1160053.
[http://dx.doi.org/10.3389/fmed.2023.1160053] [PMID: 37035335]
[47]
Akdis, M.; Aab, A.; Altunbulakli, C.; Azkur, K.; Costa, R.A.; Crameri, R.; Duan, S.; Eiwegger, T.; Eljaszewicz, A.; Ferstl, R.; Frei, R.; Garbani, M.; Globinska, A.; Hess, L.; Huitema, C.; Kubo, T.; Komlosi, Z.; Konieczna, P.; Kovacs, N.; Kucuksezer, U.C.; Meyer, N.; Morita, H.; Olzhausen, J.; O’Mahony, L.; Pezer, M.; Prati, M.; Rebane, A.; Rhyner, C.; Rinaldi, A.; Sokolowska, M.; Stanic, B.; Sugita, K.; Treis, A.; van de Veen, W.; Wanke, K.; Wawrzyniak, M.; Wawrzyniak, P.; Wirz, O.F.; Zakzuk, J.S.; Akdis, C.A. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J. Allergy Clin. Immunol., 2016, 138(4), 984-1010.
[http://dx.doi.org/10.1016/j.jaci.2016.06.033] [PMID: 27577879]
[48]
Sabir U, Gu HM, Zhang DW. Extracellular matrix turnover: Phytochemicals target and modulate the dual role of matrix metalloproteinases (MMPs) in liver fibrosis. Phytother Res 2023; 37(11): 4932-4962.
[http://dx.doi.org/10.1002/ptr.7959]
[49]
Khurana, A.; Sayed, N.; Allawadhi, P.; Weiskirchen, R. It’s all about the spaces between cells: Role of extracellular matrix in liver fibrosis. Ann. Transl. Med., 2021, 9(8), 728-728.
[http://dx.doi.org/10.21037/atm-20-2948] [PMID: 33987426]
[50]
Molière, S.; Jaulin, A.; Tomasetto, C.L.; Dali-Youcef, N. Roles of matrix metalloproteinases and their natural inhibitors in metabolism: Insights into health and disease. Int. J. Mol. Sci., 2023, 24(13), 10649.
[http://dx.doi.org/10.3390/ijms241310649] [PMID: 37445827]
[51]
Lu, W.; Qu, J.; Yan, L.; Tang, X.; Wang, X.; Ye, A.; Zou, Z.; Li, L.; Ye, J.; Zhou, L. Efficacy and safety of mesenchymal stem cell therapy in liver cirrhosis: A systematic review and meta- analysis. Stem Cell Res. Ther., 2023, 14(1), 301.
[http://dx.doi.org/10.1186/s13287-023-03518-x] [PMID: 37864199]
[52]
Pang, Q.M.; Deng, K.Q.; Zhang, M.; Wu, X.C.; Yang, R.L.; Fu, S.P.; Lin, F.Q.; Zhang, Q.; Ao, J.; Zhang, T. Multiple strategies enhance the efficacy of MSCs transplantation for spinal cord injury. Biomed. Pharmacother., 2023, 157, 114011.
[http://dx.doi.org/10.1016/j.biopha.2022.114011] [PMID: 36410123]
[53]
García-Bernal, D.; García-Arranz, M.; Yáñez, R.M.; Hervás-Salcedo, R.; Cortés, A.; Fernández-García, M.; Hernando-Rodríguez, M.; Quintana-Bustamante, Ó.; Bueren, J.A.; García-Olmo, D.; Moraleda, J.M.; Sego via, J.C.; Zapata, A.G. The current status of mesenchymal stromal cells: Controversies, unresolved issues and some promising solutions to improve their therapeutic efficacy. Front. Cell Dev. Biol., 2021, 9, 650664.
[http://dx.doi.org/10.3389/fcell.2021.650664] [PMID: 33796536]
[54]
Yuan, M.; Hu, X.; Yao, L.; Jiang, Y.; Li, L. Mesenchymal stem cell homing to improve therapeutic efficacy in liver disease. Stem Cell Res. Ther., 2022, 13(1), 179.
[http://dx.doi.org/10.1186/s13287-022-02858-4] [PMID: 35505419]
[55]
Fathy, M.; Okabe, M.; Saad Eldien, H.M.; Yoshida, T. AT-MSCs antifibrotic activity is improved by eugenol through modulation of tgf-β/smad signaling pathway in rats. Molecules, 2020, 25(2), 348.
[http://dx.doi.org/10.3390/molecules25020348] [PMID: 31952158]
[56]
Jang, Y.O.; Kim, S.H.; Cho, M.Y.; Kim, K.S.; Park, K.S.; Cha, S.K.; Kim, M.Y.; Chang, S.J.; Baik, S.K. Synergistic effects of simvastatin and bone marrow-derived mesenchymal stem cells on hepatic fibrosis. Biochem. Biophys. Res. Commun., 2018, 497(1), 264-271.
[http://dx.doi.org/10.1016/j.bbrc.2018.02.067] [PMID: 29428718]
[57]
Iwasawa, T.; Nojiri, S.; Tsuchiya, A.; Takeuchi, S.; Watanabe, T.; Ogawa, M.; Motegi, S.; Sato, T.; Kumagai, M.; Nakaya, T.; Ohbuchi, K.; Nahata, M.; Fujitsuka, N.; Takamura, M.; Terai, S. Combination therapy of Juzentaihoto and mesenchymal stem cells attenuates liver damage and regresses fibrosis in mice. Regen. Ther., 2021, 18, 231-241.
[http://dx.doi.org/10.1016/j.reth.2021.07.002] [PMID: 34409135]
[58]
Mazhari, S.; Gitiara, A.; Baghaei, K.; Hatami, B.; Rad, R.E.; Asadirad, A.; Joharchi, K.; Tokhanbigli, S.; Hashemi, S.M.; Łos, M.J.; Aghdaei, H.A.; Zali, M.R.; Ghavami, S. Therapeutic potential of bone marrow-derived mesenchymal stem cells and imatinib in a rat model of liver fibrosis. Eur. J. Pharmacol., 2020, 882, 173263.
[http://dx.doi.org/10.1016/j.ejphar.2020.173263] [PMID: 32535098]
[59]
Rafiq, H.; Ayaz, M.; Khan, H.A.; Iqbal, M.; Quraish, S.; Afridi, S.G.; Khan, A.; Khan, B.; Sher, A.; Siraj, F.; Shams, S. Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model. Braz. J. Biol., 2024, 84, e253061.
[http://dx.doi.org/10.1590/1519-6984.253061] [PMID: 35293541]
[60]
Baghaei, K.; Mazhari, S.; Tokhanbigli, S.; Parsamanesh, G.; Alavifard, H.; Schaafsma, D.; Ghavami, S. Therapeutic potential of targeting regulatory mechanisms of hepatic stellate cell activation in liver fibrosis. Drug Discov. Today, 2022, 27(4), 1044-1061.
[http://dx.doi.org/10.1016/j.drudis.2021.12.012] [PMID: 34952225]
[61]
Higashi, T.; Friedman, S.L.; Hoshida, Y. Hepatic stellate cells as key target in liver fibrosis. Adv. Drug Deliv. Rev., 2017, 121, 27-42.
[http://dx.doi.org/10.1016/j.addr.2017.05.007] [PMID: 28506744]
[62]
Guo, P.C.; Zuo, J.; Huang, K.K.; Lai, G.Y.; Zhang, X.; An, J.; Li, J.X.; Li, L.; Wu, L.; Lin, Y.T.; Wang, D.Y.; Xu, J.S.; Hao, S.J.; Wang, Y.; Li, R.H.; Ma, W.; Song, Y.M.; Liu, C.; Liu, C.Y.; Dai, Z.; Xu, Y.; Sharma, A.D.; Ott, M.; Ou-Yang, Q.; Huo, F.; Fan, R.; Li, Y.Y.; Hou, J.L.; Volpe, G.; Liu, L.Q.; Esteban, M.A.; Lai, Y.W. Cell atlas of CCl 4-induced progressive liver fibrosis reveals stage-specific responses. Zool. Res., 2023, 44(3), 451-466.
[http://dx.doi.org/10.24272/j.issn.2095-8137.2023.031] [PMID: 36994536]
[63]
Gandhi, C.R. Hepatic stellate cell activation and pro-fibrogenic signals. J. Hepatol., 2017, 67(5), 1104-1105.
[http://dx.doi.org/10.1016/j.jhep.2017.06.001] [PMID: 28939135]
[64]
Gupta, G; Khadem, F; Uzonna, JE Role of hepatic stellate cell (HSC)-derived cytokines in hepatic inflammation and immunity. Cytokine, 2019, 124, 1.
[http://dx.doi.org/10.1016/j.cyto.2018.09.004]
[65]
Martinez-Castillo, M.; Hernandez-Barragan, A.; Flores-Vasconcelos, I.; Galicia-Moreno, M.; Rosique-Oramas, D.; Perez-Hernandez, J.L.; Higuera-De la Tijera, F.; Montalvo-Jave, E.E.; Torre-Delgadillo, A.; Cordero-Perez, P.; Muñoz-Espinosa, L.; Kershenobich, D.; Gutierrez-Reyes, G. Production and activity of matrix metalloproteinases during liver fibrosis progression of chronic hepatitis C patients. World J. Hepatol., 2021, 13(2), 218-232.
[http://dx.doi.org/10.4254/wjh.v13.i2.218] [PMID: 33708351]
[66]
Geervliet, E.; Bansal, R. Matrix metalloproteinases as potential biomarkers and therapeutic targets in liver diseases. Cells, 2020, 9(5), 1212.
[http://dx.doi.org/10.3390/cells9051212] [PMID: 32414178]
[67]
Shan, L.; Wang, F.; Zhai, D.; Meng, X.; Liu, J.; Lv, X. Matrix metalloproteinases induce extracellular matrix degradation through various pathways to alleviate hepatic fibrosis. Biomed. Pharmacother., 2023, 161, 114472.
[http://dx.doi.org/10.1016/j.biopha.2023.114472] [PMID: 37002573]
[68]
Pistelli, L.; Sansone, C.; Smerilli, A.; Festa, M.; Noonan, D.M.; Albini, A.; Brunet, C. Mmp-9 and il-1β as targets for diatoxanthin and related microalgal pigments: Potential chemopreventive and photoprotective agents. Mar. Drugs, 2021, 19(7), 354.
[http://dx.doi.org/10.3390/md19070354] [PMID: 34206447]
[69]
Luo, X.Y.; Meng, X.J.; Cao, D.C.; Wang, W.; Zhou, K.; Li, L.; Guo, M.; Wang, P. Transplantation of bone marrow mesenchymal stromal cells attenuates liver fibrosis in mice by regulating macrophage subtypes. Stem Cell Res. Ther., 2019, 10(1), 16.
[http://dx.doi.org/10.1186/s13287-018-1122-8] [PMID: 30635047]
[70]
Li, Y.; Fan, W.; Link, F.; Wang, S.; Dooley, S. Transforming growth factor β latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease. JHEP Reports, 2022, 4(2), 100397.
[http://dx.doi.org/10.1016/j.jhepr.2021.100397] [PMID: 35059619]
[71]
Kisseleva, T.; Brenner, D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat. Rev. Gastroenterol. Hepatol., 2021, 18(3), 151-166.
[http://dx.doi.org/10.1038/s41575-020-00372-7] [PMID: 33128017]
[72]
Wang, P.; Cui, Y.; Wang, J.; Liu, D.; Tian, Y.; Liu, K.; Wang, X.; Liu, L.; He, Y.; Pei, Y.; Li, L.; Sun, L.; Zhu, Z.; Chang, D.; Jia, J.; You, H. Mesenchymal stem cells protect against acetaminophen hepatotoxicity by secreting regenerative cytokine hepatocyte growth factor. Stem Cell Res. Ther., 2022, 13(1), 94.
[http://dx.doi.org/10.1186/s13287-022-02754-x] [PMID: 35246254]
[73]
Zhao, Y.; Ye, W.; Wang, Y.D.; Chen, W.D. HGF/c-Met: A key promoter in liver regeneration. Front. Pharmacol., 2022, 13, 808855.
[http://dx.doi.org/10.3389/fphar.2022.808855] [PMID: 35370682]
[74]
Wang, Z.; Du, K.; Jin, N.; Tang, B.; Zhang, W. Macrophage in liver Fibrosis: Identities and mechanisms. Int. Immunopharmacol., 2023, 120, 110357.
[http://dx.doi.org/10.1016/j.intimp.2023.110357] [PMID: 37224653]
[75]
Song, Y.; Zhang, T.J.; Li, Y.; Gao, Y. Mesenchymal stem cells decrease M1/M2 ratio and alleviate inflammation to improve limb ischemia in mice. Med. Sci. Monit., 2020, 26, e923287.
[http://dx.doi.org/10.12659/MSM.923287] [PMID: 32860388]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy