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Communication Open Access

Established Hepatic Stellate Cell Lines in Hepatology Research

Fibrosis. 2023, 1(1), 10003; https://doi.org/10.35534/fibrosis.2023.10003
Ralf Weiskirchen 1 *   
1
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany
*
Authors to whom correspondence should be addressed.

Received: 06 Feb 2023    Accepted: 17 Mar 2023    Published: 21 Mar 2023   

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Abstract

Hepatic stellate cells comprise a minor cell population in the liver that plays a key role in the pathogenesis of hepatic fibrosis. In chronic liver damage, they undergo a transition from a quiescent to a highly proliferative phenotype with the capacity to synthesize large quantities of extracellular matrix compounds such as collagens. Because of their pivotal role in liver disease pathogenesis, this hepatic cell population has become into the focus of liver research for many years. However, the isolation of these cells is time consuming and requires trained laboratory personnel. In addition, working with primary cells requires the following of ethical and legal standards that need to be approved by the respective authorities. Therefore, continuous growing hepatic stellate cells have become very popular in research laboratories because they are widely available, easy to handle, allow a continuous supply of materials, and further allow reduction of lab animal use in biomedical research. This communication provides some general information about immortalized hepatic stellate cell lines from mouse, rats and humans.

Keywords

Cell culture; Cell lines; Hepatic stellate cells; Myofibroblasts; Liver; Fibrosis; In vitro; Translational research

References

1.
Acharya P, Chouhan K, Weiskirchen S, Weiskirchen R. Cellular mechanisms of liver fibrosis.  Front. Pharmacol. 2021, 12, 671640. [Google Scholar]
2.
Meurer SK, Weiskirchen S, Tag CG, Weiskirchen R. Isolation, purification, and culture of primary murine hepatic stellate cells: An update.  Methods Mol. Biol. 2023, 2669, in press. doi:10.1007/978-1-0716-3207-9_1 [Google Scholar]
3.
Russell WMS, Burch R. The Principles of Humane Experimental Technique; Methuen: London, UK, 1959.
4.
Nanda I, Schröder SK, Steinlein C, Haaf T, Buhl EM, Grimm DG, et al. Rat hepatic stellate cell line CFSC-2G: Genetic markers and short tandem repeat profile useful for cell line authentication.  Cells 2022, 11, 2900. [Google Scholar]
5.
Nanda I, Steinlein C, Haaf T, Buhl EM, Grimm DG, Friedman SL, et al. Genetic characterization of rat hepatic stellate cell line HSC-T6 for in vitro cell line authentication.  Cells 2022, 11, 1783. [Google Scholar]
6.
Friedman SL, Weiskirchen R. Working with immortalized hepatic stellate cell lines.  Methods Mol. Biol. 2023, 2669, in press. [Google Scholar]
7.
Merck SCC613—LX-2 Cas9 Human Hepatic Stellate Cell Line. Available online: https://www.emdmillipore.com/US/en/product/LX-2-Cas9-Human-Hepatic-Stellate-Cell-Line,MM_NF-SCC613?ReferrerURL=https%3A%2F%2Fwww.google.com%2F (accessed on 17 March 2023).
8.
González-Cuevas J, Bueno-Topete M, Armendariz-Borunda J. Urokinase plasminogen activator stimulates function of active forms of stromelysin and gelatinases (MMP-2 and MMP-9) in cirrhotic tissue.  J. Gastroenterol. Hepatol. 2006, 21, 1544–1554. [Google Scholar]
9.
International Cell Line Authentication Committee (ICLAC) Register of Misidentified Cell Lines. Available online: https://iclac.org/ (accessed on 17 March 2023).
10.
Borojevic R, Monteiro AN, Vinhas SA, Domont GB, Mourão PA, Emonard H, et al. Establishment of a continuous cell line from fibrotic schistosomal granulomas in mice livers.  In Vitro Cell Dev. Biol. 1985, 21, 382–390. [Google Scholar]
11.
Schröder SK, Schüler HM, Petersen KV, Tesauro C, Knudsen BR, Pedersen FS, et al. Genetic and molecular characterization of the immortalized murine hepatic stellate cell line GRX.  Cells 2022, 11, 1504. [Google Scholar]
12.
Vogel S, Piantedosi R, Frank J, Lalazar A, Rockey DC, Friedman SL, et al. An immortalized rat liver stellate cell line (HSC-T6): A new cell model for the study of retinoid metabolism in vitro. J. Lipid Res. 2000, 41, 882–893. [Google Scholar]
13.
Greenwel P, Schwartz M, Rosas M, Peyrol S, Grimaud JA, Rojkind M. Characterization of fat-storing cell lines derived from normal and CCl4-cirrhotic livers. Differences in the production of interleukin-6.  Lab. Invest. 1991, 65, 644–653. [Google Scholar]
14.
Greenwel P, Rubin J, Schwartz M, Hertzberg EL, Rojkind M. Liver fat-storing cell clones obtained from a CCl4-cirrhotic rat are heterogeneous with regard to proliferation, expression of extracellular matrix components, interleukin-6, and connexin 43.  Lab. Invest. 1993, 69, 210–216. [Google Scholar]
15.
Xu L, Hui AY, Albanis E, Arthur MJ, O’Byrne SM, Blaner WS, et al. Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis.  Gut 2005, 54, 142–151. [Google Scholar]
16.
Weiskirchen R, Weimer J, Meurer SK, Kron A, Seipel B, Vater I, et al. Genetic characteristics of the human hepatic stellate cell line LX-2.  PLoS ONE 2013, 8, e75692. [Google Scholar]
17.
Sohara N, Znoyko I, Levy MT, Trojanowska M, Reuben A. Reversal of activation of human myofibroblast-like cells by culture on a basement membrane-like substrate.  J. Hepatol. 2002, 37, 214–221. [Google Scholar]
18.
Senoo H, Imai K, Sato M, Kojima N, Miura M, Hata R. Three-dimensional structure of extracellular matrix reversibly regulates morphology, proliferation and collagen metabolism of perisinusoidal stellate cells (vitamin A-storing cells).  Cell Biol. Int. 1996, 20, 501–512. [Google Scholar]
19.
Abergel A, Sapin V, Dif N, Chassard C, Darcha C, Marcand-Sauvant J, et al. Growth arrest and decrease of alpha-SMA and type I collagen expression by palmitic acid in the rat hepatic stellate cell line PAV-1.  Dig. Dis. Sci. 2006, 51, 986–995. [Google Scholar]
20.
Guo M, Wang Z, Dai J, Fan H, Yuan N, Gao L, et al. Glycyrrhizic acid alleviates liver fibrosis in vitro and in vivo via activating CUGBP1-mediated IFN-γ/STAT1/Smad7 pathway.  Phytomedicine 2022, 112, 154587. [Google Scholar]
21.
Gong Q, Zeng Z, Jiang T, Bai X, Pu C, Hao Y, 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. [Google Scholar]
22.
Xue T, Yue L, Zhu G, Tan Z, Liu H, Gan C, et al. An oral phenylacrylic acid derivative suppressed hepatic stellate cell activation and ameliorated liver fibrosis by blocking TGF-β1 signalling.  Liver Int. 2023, 43, 718–732. [Google Scholar]
23.
Ying H, Li L, Zhao Y, Ni F. Ivermectin attenuates CCl4-induced liver fibrosis in mice by suppressing hepatic stellate cell activation.  Int. J. Mol. Sci. 2022, 23, 16043. [Google Scholar]
24.
Weiskirchen R. Hepatoprotective and anti-fibrotic agents: It’s time to take the next step.  Front. Pharmacol. 2016, 6, 303. [Google Scholar]
25.
The Human Protein Atlas. The Open Access Resource for Human Proteins. Available online: https://www.proteinatlas.org/ (accessed on 17 March 2023).
26.
Sauvant P, Sapin V, Abergel A, Schmidt CK, Blanchon L, Alexandre-Gouabau MC, et al. PAV-1, a new rat hepatic stellate cell line converts retinol into retinoic acid, a process altered by ethanol.  Int. J. Biochem. Cell Biol. 2002, 34, 1017–1029. [Google Scholar]
27.
Weiskirchen R, Kneifel J, Weiskirchen S, van de Leur E, Kunz D, Gressner AM. Comparative evaluation of gene delivery devices in primary cultures of rat hepatic stellate cells and rat myofibroblasts.  BMC Cell Biol. 2000, 1, 4. [Google Scholar]
28.
Pinzani M, Gesualdo L, Sabbah GM, Abboud HE. Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells.  J. Clin. Invest. 1989, 84, 1786–1793. [Google Scholar]
29.
Borkham-Kamphorst E, van Roeyen CR, Ostendorf T, Floege J, Gressner AM, Weiskirchen R. Pro-fibrogenic potential of PDGF-D in liver fibrosis. J. Hepatol. 2007, 46, 1064–1074. [Google Scholar]
30.
Magness ST, Bataller R, Yang L, Brenner DA. A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic fibrogenic cell populations.  Hepatology 2004, 40, 1151–1159. [Google Scholar]
31.
Filliol A, Saito Y, Nair A, Dapito DH, Yu LX, Ravichandra A, et al. Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis.  Nature 2022, 610, 356–365. [Google Scholar]
32.
Krenkel O, Hundertmark J, Ritz TP, Weiskirchen R, Tacke F. Single cell RNA sequencing identifies subsets of hepatic stellate cells and myofibroblasts in liver fibrosis.  Cells 2019, 8, 503. [Google Scholar]
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