A Bioreactor Technology for Modeling Fibrosis in Human and Rodent Precision‐Cut Liver Slices
Open accessPublished version of a preprint
Abstract
Precision cut liver slices (PCLSs) retain the structure and cellular composition of the native liver and represent an improved system to study liver fibrosis compared to two‐dimensional mono‐ or co‐cultures. The aim of this study was to develop a bioreactor system to increase the healthy life span of PCLSs and model fibrogenesis. PCLSs were generated from normal rat or human liver, or fibrotic rat liver, and cultured in our bioreactor. PCLS function was quantified by albumin enzyme‐linked immunosorbent assay (ELISA). Fibrosis was induced in PCLSs by transforming growth factor beta 1 (TGFβ1) and platelet‐derived growth factor (PDGFββ) stimulation ± therapy. Fibrosis was assessed by gene expression, picrosirius red, and α‐smooth muscle actin staining, hydroxyproline assay, and soluble ELISAs. Bioreactor‐cultured PCLSs are viable, maintaining tissue structure, metabolic activity, and stable albumin secretion for up to 6 days under normoxic culture conditions. Conversely, standard static transwell‐cultured PCLSs rapidly deteriorate, and albumin secretion is significantly impaired by 48 hours. TGFβ1/PDGFββ stimulation of rat or human PCLSs induced fibrogenic gene expression, release of extracellular matrix proteins, activation of hepatic myofibroblasts, and histological fibrosis. Fibrogenesis slowly progresses over 6 days in cultured fibrotic rat PCLSs without exogenous challenge. Activin receptor‐like kinase 5 (Alk5) inhibitor (Alk5i), nintedanib, and obeticholic acid therapy limited fibrogenesis in TGFβ1/PDGFββ‐stimulated PCLSs, and Alk5i blunted progression of fibrosis in fibrotic PCLS. Conclusion: We describe a bioreactor technology that maintains functional PCLS cultures for 6 days. Bioreactor‐cultured PCLSs can be successfully used to model fibrogenesis and demonstrate efficacy of antifibrotic therapies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PCLS cultures are approximately 200 micron-thick tissue slices from liver core biopsy that maintain cell identity and tissue structure for several days under specialized conditions.
“As a perhaps simpler alternative to organ-on-chip systems, PCLS cultures are ~200 micron-thick tissue slices cut out of a liver core biopsy that has been shown to maintain cell identity and tissue structure for several days when cultured under specialized conditions (248)(249).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [249]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280 · see citing works
Pathobiology of liver fibrosis: a translational success story
Lee, Y. A., Wallace, M. C., & Friedman, S. L. (2015) · Gut · doi:10.1136/gutjnl-2014-306842 · Cited by 894 · see citing works
de Graaf, I. A. M., Olinga, P., de Jager, M. H., Merema, M. T., de Kanter, R., van de Kerkhof, E. G., & Groothuis, G. M. M. (2010) · Nature Protocols · doi:10.1038/nprot.2010.111 · Cited by 409 · see citing works
Hepatic stellate cells require a stiff environment for myofibroblastic differentiation
Olsen, A. L., Bloomer, S. A., Chan, E. P., Gaça, M. D. A., Georges, P. C., Sackey, B., Uemura, M., Janmey, P. A., & Wells, R. G. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00412.2010 · Cited by 355 · see citing works
Elaut, G., Henkens, T., Papeleu, P., Snykers, S., Vinken, M., Vanhaecke, T., & Rogiers, V. (2006) · Current Drug Metabolism · doi:10.2174/138920006778017759 · Cited by 292 · see citing works
Oakley, F., Meso, M., Iredale, J. P., Green, K., Marek, C. J., Zhou, X., May, M. J., Millward‐Sadler, H., Wright, M. C., & Mann, D. A. (2005) · Gastroenterology · doi:10.1053/j.gastro.2004.10.003 · Cited by 265 · see citing works
Self-citationMcHutchison, J. G., Blatt, L. M., de Medina, M. D., Craig, J. R., Conrad, A. J., Schiff, E. R., Tong, M. J., & The Consensus Interferon Study Group (2000) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.2000.02233.x · Cited by 228 · see citing works
Grygielko, E. T., Martin, W. M., Tweed, C. W., Thornton, P., Harling, J. D., Brooks, D. P., & Laping, N. J. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.082099 · Cited by 193 · see citing works
Animal models for the study of hepatic fibrosis
Stärkel, P., & Leclercq, I. A. (2011) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2011.02.004 · Cited by 178 · see citing works
Animal Models for Fibrotic Liver Diseases: What We Have, What We Need, and What Is under Development
Delire, B., Stärkel, P., & Leclercq, I. A. (2015) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2014.00035 · Cited by 171 · see citing works
Bhogal, R. H., Hodson, J. A., Bartlett, D. C., Weston, C. J., Curbishley, S. M., Shepherd, E. L., Williams, K. T., Reynolds, G. M., Newsome, P. N., Adams, D., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018222 · Cited by 135 · see citing works
van Midwoud, P. M., Groothuis, G. M. M., Merema, M. T., & Verpoorte, E. M. J. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22516 · Cited by 135 · see citing works
Lichtinghagen, R., Michels, D., Haberkorn, C. I., Arndt, B., Bahr, M., Flemming, P., Manns, M. P., & Boeker, K. H. W. (2001) · Journal of Hepatology · doi:10.1016/s0168-8278(00)00037-4 · Cited by 123 · see citing works
Nuclear Factor-κB1 (p50) Limits the Inflammatory and Fibrogenic Responses to Chronic Injury
Oakley, F., Mann, J., Nailard, S., Smart, D. E., Mungalsingh, N., Constandinou, C., Ali, S., Wilson, S. J., Millward-Sadler, H., Iredale, J. P., et al. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62291-2 · Cited by 123 · see citing works
Self-citationRocha, M. C., Grady, J. P., Grünewald, A., Vincent, A. E., Dobson, P. F., Taylor, R. W., Turnbull, D. M., & Rygiel, K. A. (2015) · Scientific Reports · doi:10.1038/srep15037 · Cited by 121 · see citing works
Precision-cut liver slices: A tool to model the liver ex vivo
Olinga, P., & Schuppan, D. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.01.009 · Cited by 119 · see citing works
Enzan, H., Hara, H., Himeno, H., Iwamura, S., Saibara, T., Onishi, S., & Yamamoto, Y. (1994) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf00194608 · Cited by 118 · see citing works
Güvendiren, M., Perepelyuk, M., Wells, R. G., & Burdick, J. A. (2013) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2013.11.008 · Cited by 103 · see citing works
Comparison of five incubation systems for rat liver slices using functional and viability parameters
Olinga, P., Groen, K., Hof, I. H., de Kanter, R., Koster, H. J., Leeman, W. R., Rutten, A. A. J. J. L., van Twillert, K., & Groothuis, G. M. M. (1997) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/s1056-8719(97)00060-9 · Cited by 102 · see citing works
Quantitative Assessment of Macrophage Functions in Repair and Fibrosis
Wynn, T., Barron, L., Thompson, R. W., Madala, S., Wilson, M. S., Cheever, A., & Ramalingam, T. (2011) · Current Protocols in Immunology · doi:10.1002/0471142735.im1422s93 · Cited by 100 · see citing works
Alcohol directly stimulates epigenetic modifications in hepatic stellate cells
Page, A., Paoli, P. P., Hill, S. J., Howarth, R., Wu, R. P., Kweon, S.-M., French, J., White, S. A., Tsukamoto, H., Mann, D. A., et al. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.09.033 · Cited by 96 · see citing works
Self-citationIjssennagger, N., Janssen, A. W. F., Milona, A., Pittol, J. M. R., Hollman, D. A. A., Mokrý, M., Betzel, B., Berends, F. J., Janssen, I. M. C., van Mil, S. W. C., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.01.016 · Cited by 93 · see citing works
Precision-cut human liver slice cultures as an immunological platform
Wu, X., Roberto, J. B., Knupp, A., Kenerson, H. L., Truong, C. D., Yuen, S. Y., Brempelis, K. J., Tuefferd, M., Chen, A., Horton, H., et al. (2018) · Journal of Immunological Methods · doi:10.1016/j.jim.2018.01.012 · Cited by 81 · see citing works
Yilmaz, Y. N., & Eren, F. (2018) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000001240 · Cited by 62 · see citing works
Engineering in vitro models of hepatofibrogenesis
Mazza, G., Al‐Akkad, W., & Rombouts, K. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.05.018 · Cited by 59 · see citing works
Evaluation of fibrosis in precision-cut tissue slices
Westra, I. M., Pham, B. T., Groothuis, G. M. M., & Olinga, P. (2012) · Xenobiotica · doi:10.3109/00498254.2012.723151 · Cited by 49 · see citing works
van de Bovenkamp, M., Groothuis, G. M. M., Meijer, D. K. F., & Olinga, P. (2008) · Toxicology in Vitro · doi:10.1016/j.tiv.2007.11.019 · Cited by 48 · see citing works
Ando, W., Yokomori, H., Tsutsui, N., Yamanouchi, E., Suzuki, Y., Oda, M., Inagaki, Y., Otori, K., & Okazaki, I. (2017) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2017.0030 · Cited by 43 · see citing works
Starokozhko, V., Vatakuti, S., Schievink, B., Merema, M. T., Asplund, A., Synnergren, J., Aspegren, A., & Groothuis, G. M. M. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1865-x · Cited by 38 · see citing works
Irvine, K. M., Wockner, L. F., Hoffmann, I., Horsfall, L. U., Fagan, K. J., Bijin, V. A., Lee, B. T. K., Clouston, A. D., Lampe, G., Connolly, J. E., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167001 · Cited by 36 · see citing works
Koch, A., Saran, S., Tran, D. D. H., Klebba-Färber, S., Thiesler, H., Sewald, K., Schindler, S., Braun, A. C., Klopfleisch, R., & Tamura, T. (2014) · Cell Communication and Signaling · doi:10.1186/s12964-014-0073-7 · Cited by 31 · see citing works
Granitzny, A., Knebel, J., Schaudien, D., Braun, A. C., Steinberg, P., Dasenbrock, C., & Hansen, T. (2017) · Toxicology in Vitro · doi:10.1016/j.tiv.2017.05.001 · Cited by 28 · see citing works
Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model
Lagaye, S., Brun, S., Gaston, J., Shen, H., Stránská, R., Camus, C., Dubray, C., Rousseau, G., Massault, P. P., Courcambeck, J., et al. (2016) · World Journal of Hepatology · doi:10.4254/wjh.v8.i21.902 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Emerging therapeutic opportunities for integrin inhibitors
Slack, R. J., Macdonald, S. J. F., Roper, J. A., Jenkins, G. R., & Hatley, R. J. D. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00284-4 · Cited by 550 · see citing works
Hepatic fibrosis 2022: Unmet needs and a blueprint for the future
Friedman, S. L., & Pinzani, M. (2022) · Hepatology · doi:10.1002/hep.32285 · Cited by 430 · see citing works
Pakshir, P., Noskovicova, N., Lodyga, M., Son, D. O., Schuster, R., Goodwin, A., Karvonen, H., & Hinz, B. (2020) · Journal of Cell Science · doi:10.1242/jcs.227900 · Cited by 293 · see citing works
Tumour extracellular vesicles and particles induce liver metabolic dysfunction
Wang, G., Li, J., Bojmar, L., Chen, H., Li, Z., Tobias, G. C., Hu, M., Homan, E. A., Lucotti, S., Zhao, F., et al. (2023) · Nature · doi:10.1038/s41586-023-06114-4 · Cited by 275 · see citing works
Weaver, R. J., Blomme, E. A. G., Chadwick, A. E., Copple, I. M., Gerets, H. H. J., Goldring, C. E., Guillouzo, A., Hewitt, P. G., Ingelman‐Sundberg, M., Jensen, K. G., et al. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0048-x · Cited by 254 · see citing works
Mechanical communication in fibrosis progression
Long, Y., Niu, Y., Liang, K., & Du, Y. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.10.002 · Cited by 233 · see citing works
Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner
Lagnado, A., Leslie, J., Ruchaud‐Sparagano, M., Victorelli, S., Hirsova, P., Ogrodnik, M., Collins, A. L., Vizioli, M. G., Habiballa, L., Saretzki, G., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2020106048 · Cited by 211 · see citing works
Self-citationThe landscape of gene mutations in cirrhosis and hepatocellular carcinoma
Müller, M., Bird, T. G., & Nault, J. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.01.019 · Cited by 178 · see citing works
Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH)
Wang, S., & Friedman, S. L. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adi0759 · Cited by 158 · see citing works
The therapeutic potential of galectin-3 inhibition in fibrotic disease
Slack, R. J., Mills, R., & Mackinnon, A. C. (2021) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2020.105881 · Cited by 136 · see citing works
Ammonia Scavenging Prevents Progression of Fibrosis in Experimental Nonalcoholic Fatty Liver Disease
Chiara, F. D., Thomsen, K. L., Habtesion, A., Jones, H., Davies, N. A., Gracia‐Sancho, J., Manicardi, N., Hall, A. R., Andreola, F., Paish, H. L., et al. (2019) · Hepatology · doi:10.1002/hep.30890 · Cited by 102 · see citing works
Self-citationBárcena‐Varela, M., Paish, H. L., Alvarez, L., Uriarte, I., Latasa, M. U., Santamaría, E., Recalde, M., Garate, M., Clavería-Cabello, A., Colyn, L., et al. (2020) · Gut · doi:10.1136/gutjnl-2019-320205 · Cited by 96 · see citing works
Self-citationBioengineered 3D Models to Recapitulate Tissue Fibrosis
Sacchi, M., Bansal, R., & Rouwkema, J. (2020) · Trends in biotechnology · doi:10.1016/j.tibtech.2019.12.010 · Cited by 91 · see citing works
Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ
Kiourtis, C., Terradas-Terradas, M., Gee, L., May, S., Γεωργακοπούλου, Α., Collins, A., O'Sullivan, E. D., Baird, D., Hassan, M., Shaw, R., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01543-3 · Cited by 85 · see citing works
Self-citationMacia, M. G., Santos‐Ledo, A., Leslie, J., Paish, H. L., Collins, A., Scott, R., Watson, A. A., Burgoyne, R. A., White, S. A., French, J., et al. (2021) · Hepatology · doi:10.1002/hep.32048 · Cited by 76 · see citing works
Self-citationAntifibrotic therapy in nonalcoholic steatohepatitis: time for a human-centric approach
Brennan, P. N., Elsharkawy, A. M., Kendall, T. J., Loomba, R., Mann, D. A., & Fallowfield, J. A. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00796-x · Cited by 68 · see citing works
Self-citationIn Vitro Models for the Study of Liver Biology and Diseases: Advances and Limitations
Kaur, S., Kidambi, S., Ortega‐Ribera, M., Thủy, L. T. T., Nieto, N., Cogger, V. C., Xie, W., Tacke, F., & Gracia‐Sancho, J. (2022) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2022.11.008 · Cited by 67 · see citing works
Best Practices and Progress in Precision-Cut Liver Slice Cultures
Dewyse, L., Reynaert, H., & van Grunsven, L. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137137 · Cited by 63 · see citing works
Ströbel, S., Kostadinova, R. M., Fiaschetti‐Egli, K., Rupp, J., Bieri, M., Pawłowska, A., Busler, D., Hofstetter, T., Sanchez, K., Grepper, S., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-01951-7 · Cited by 58 · see citing works
Romualdo, G. R., Leroy, K., Costa, C. J. S., Bacil, G. P., Vanderborght, B., da Silva, T. C., Barbisan, L. F., Andraus, W., Devisscher, L., Câmara, N. O. S., et al. (2021) · Cancers · doi:10.3390/cancers13215583 · Cited by 52 · see citing works
Lyall, M. J., Thomson, J. P., Cartier, J., Ottaviano, R., Kendall, T. J., Meehan, R. R., & Drake, A. J. (2019) · Epigenetics · doi:10.1080/15592294.2019.1649527 · Cited by 49 · see citing works
Jagatia, R., Doornebal, E. J., Rastovic, U., Harris, N., Feyide, M., Lyons, A. M., Miquel, R., Zen, Y., Zamalloa, A., Malik, F., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104826 · Cited by 43 · see citing works
Xu, M., Warner, C., Duan, X., Cheng, Z., Jeyarajan, A. J., Li, W., Wang, Y., Shao, T., Salloum, S., Chen, P., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.01.026 · Cited by 41 · see citing works
Lehmann, M., Krishnan, R., Sucre, J. M. S., Kulkarni, H. S., Pineda, R., Anderson, C., Banovich, N. E., Behrsing, H. P., Dean, C. H., Haak, A. J., et al. (2024) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2024-0479st · Cited by 45 · see citing works
Emerging synthetic drugs for the treatment of liver cirrhosis
Fallowfield, J. A., Ramos, M. J., & Robertson, A. (2021) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2021.1918099 · Cited by 38 · see citing works
c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis
Leslie, J., Macia, M. G., Luli, S., Worrell, J. C., Reilly, W. J., Paish, H. L., Knox, A., Barksby, B. S., Gee, L., Zaki, M. Y. W., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00306-2 · Cited by 36 · see citing works
Self-citationDynamic Physiological Culture of Ex Vivo Human Tissue: A Systematic Review
Hughes, D. L., Hughes, A., Soonawalla, Z. F., Mukherjee, S., & O’Neill, E. (2021) · Cancers · doi:10.3390/cancers13122870 · Cited by 33 · see citing works
A new NRF2 activator for the treatment of human metabolic dysfunction-associated fatty liver disease
Hammoutène, A., Laouirem, S., Albuquerque, M., Colnot, N., Brzustowski, A., Valla, D. C., Provost, N., Delerive, P., & Paradis, V. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100845 · Cited by 32 · see citing works
Mannaerts, I., Eysackers, N., van Os, E. A., Verhulst, S., Roosens, T., Smout, A., Hierlemann, A. R., Frey, O., Leite, S. B., & van Grunsven, L. A. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120335 · Cited by 32 · see citing works
Sukei, T., Palma, E., & Urbani, L. (2021) · Cancers · doi:10.3390/cancers13215586 · Cited by 29 · see citing works
Jiang, J., Pieterman, C., Ertaylan, G., Peeters, R., & de Kok, T. M. C. M. (2019) · Archives of Toxicology · doi:10.1007/s00204-019-02585-5 · Cited by 31 · see citing works
Hoyle, H. W., Stenger, C. M. L., & Przyborski, S. A. (2022) · Biomaterials and Biosystems · doi:10.1016/j.bbiosy.2022.100063 · Cited by 30 · see citing works
Recent advance of in vitro models in natural phytochemicals absorption and metabolism
Huang, Y., Chen, Y., Lu, S., & Zhao, C. (2021) · eFood · doi:10.53365/efood.k/146945 · Cited by 27 · see citing works
Animal and Human Models of Tissue Repair and Fibrosis: An Introduction
Lagares, D., & Hinz, B. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1382-5_20 · Cited by 23 · see citing works
NAFLD-Related HCC: Focus on the Latest Relevant Preclinical Models
Fang, J., Celton‐Morizur, S., & Desdouets, C. (2023) · Cancers · doi:10.3390/cancers15143723 · Cited by 24 · see citing works
Spatial lipidomics reveals sphingolipid metabolism as anti-fibrotic target in the liver
Gruevska, A., Leslie, J., Perpiñán, E., Maude, H., Collins, A., Johnson, S., Evangelista, L., Sabey, E., French, J., White, S., et al. (2025) · Metabolism · doi:10.1016/j.metabol.2025.156237 · Cited by 23 · see citing works
Self-citationLeslie, J., Krishnamurthy, K. A., Gopalsamy, I. K., Inácio, P., Huch, M., Gallage, S., Oakley, F., & Vacca, M. (2026) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01162-9 · Cited by 25 · see citing works
Self-citationImproved Precision-Cut Liver Slice Cultures for Testing Drug-Induced Liver Fibrosis
Dewyse, L., Smet, V. D., Verhulst, S., Eysackers, N., Kunda, R., Messaoudi, N., Reynaert, H., & van Grunsven, L. A. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.862185 · Cited by 23 · see citing works
Kostadinova, R. M., Ströbel, S., Chen, L., Fiaschetti‐Egli, K., Gadient, J., Pawlowska, A., Petitjean, L., Bieri, M., Thoma, E., & Petitjean, M. (2024) · Scientific Reports · doi:10.1038/s41598-024-55438-2 · Cited by 21 · see citing works
Wang, Y., Leaker, B. D., Qiao, G., Sojoodi, M., Eissa, I. R., Epstein, E. T., Eddy, J., Dimowo, O., Lauer, G. M., Qadan, M., et al. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000558 · Cited by 22 · see citing works
In vitro cell-based models of drug-induced hepatotoxicity screening: progress and limitation
Mirahmad, M., Sabourian, R., Mahdavi, M. R., Larijani, B. A., & Safavi, M. (2022) · Drug Metabolism Reviews · doi:10.1080/03602532.2022.2064487 · Cited by 20 · see citing works
Hepatocyte cultures: From collagen gel sandwiches to microfluidic devices with integrated biosensors
de Hoyos‐Vega, J. M., Hong, H. J., Stybayeva, G., & Revzin, A. (2021) · APL Bioengineering · doi:10.1063/5.0058798 · Cited by 20 · see citing works
Bhattacharya, D., Becker, C., Readhead, B. P., Goossens, N., Buros, J. L., Fiel, M. I., Cousens, L. P., Magnusson, B., Backmark, A., Hicks, R., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-99008-2 · Cited by 20 · see citing works
In vitro modeling of liver fibrosis in 3D microtissues using scalable micropatterning system
Zahmatkesh, E., Othman, A., Braun, B., Aspera-Werz, R. H., Ruoß, M., Piryaei, A., Vosough, M., & Nussler, A. K. (2022) · Archives of Toxicology · doi:10.1007/s00204-022-03265-7 · Cited by 20 · see citing works
Implementation of pre-clinical methodologies to study fibrosis and test anti-fibrotic therapy
Oakley, F., Gee, L., Sheerin, N., & Borthwick, L. A. (2019) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2019.10.004 · Cited by 17 · see citing works
Self-citationA Microfluidic Device for Long‐Term Maintenance of Organotypic Liver Cultures
de Hoyos‐Vega, J. M., Hong, H. J., Loutherback, K., Stybayeva, G., & Revzin, A. (2022) · Advanced Materials Technologies · doi:10.1002/admt.202201121 · Cited by 16 · see citing works
Global 13C tracing and metabolic flux analysis of intact human liver tissue ex vivo
Grankvist, N., Jönsson, C., Hedin, K., Sundqvist, N., Sandström, P., Björnsson, B., Begzati, A., Mickols, E., Artursson, P., Jain, M., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01119-3 · Cited by 17 · see citing works
Precision-cut liver slices as an alternative method for long-term hepatotoxicity studies
Othman, A., Ehnert, S., Dropmann, A., Ruoß, M., Nussler, A. K., & Hammad, S. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02861-9 · Cited by 16 · see citing works
Human Precision-Cut Liver Slices: A Potential Platform to Study Alcohol-Related Liver Disease
Rastovic, U., Bozzano, S. F., Riva, A., Nieves, A. S., Harris, N., Miquel, R., Lackner, C., Zen, Y., Zamalloa, A., Menon, K. V., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010150 · Cited by 16 · see citing works
Hoyle, H. W., Smith, L. A., Williams, R. J., & Przyborski, S. A. (2020) · Interface Focus · doi:10.1098/rsfs.2019.0090 · Cited by 16 · see citing works
Chronic liver diseases: From development to novel pharmacological therapies: IUPHAR Review 37
Borrello, M. T., & Mann, D. A. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15853 · Cited by 15 · see citing works
Self-citationKamat, V., Grumbine, M. K., Bao, K., Mokate, K., Khalil, G. I., Cook, D., Clearwater, B., Hirst, R. V., Harman, J. C., Boeck, M., et al. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100642 · Cited by 9 · see citing works
Gallego‐Durán, R., Albillos, A., Ampuero, J., Arechederra, M., Bañares, R., Blas‐García, A., Berná, G., Caparrós, E., Delgado, T. C., Falcón‐Pérez, J. M., et al. (2022) · Gastroenterología y Hepatología · doi:10.1016/j.gastrohep.2022.02.005 · Cited by 12 · see citing works
Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats
Leaker, B. D., Wang, Y., Tam, J., & Anderson, R. R. (2024) · Scientific Reports · doi:10.1038/s41598-024-66235-2 · Cited by 11 · see citing works
Bioengineered Liver Models for Investigating Disease Pathogenesis and Regenerative Medicine
Kukla, D. A., & Khetani, S. R. (2021) · Seminars in Liver Disease · doi:10.1055/s-0041-1731016 · Cited by 11 · see citing works
Rezania, V., Coombe, D., & Tuszyński, J. A. (2020) · Journal of Functional Biomaterials · doi:10.3390/jfb11010013 · Cited by 11 · see citing works
Chidlow, S. J., Randle, L. E., & Kelly, R. (2022) · PLoS ONE · doi:10.1371/journal.pone.0275788 · Cited by 10 · see citing works
Valente, L. C., Bacil, G. P., Riechelmann-Casarin, L., Barbosa, G. C., Barbisan, L. F., & Romualdo, G. R. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122781 · Cited by 9 · see citing works
Zheng, Q., Zhong, X. Y., Kang, Q., Zhang, Z., Ren, D., Liu, Y., & Rui, L. (2025) · Advanced Science · doi:10.1002/advs.202417355 · Cited by 9 · see citing works
Zaki, M. Y. W., Shetty, S., Wilkinson, A. L., Patten, D. A., Oakley, F., & Reeves, H. L. (2021) · Journal of Visualized Experiments · doi:10.3791/62868 · Cited by 8 · see citing works
Self-citationZhai, Y., Chavez, J. A., D’Aquino, K. E., Meng, R., Nawrocki, A. R., Pocai, A., Wang, L., & Ma, L.-J. (2024) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00445.2023 · Cited by 8 · see citing works
Chen, J., Martín‐Mateos, R., Li, J., Yin, Z., Chen, J., Lü, X., Glaser, K. J., Mounajjed, T., Yashiro, H., Siegelman, J., et al. (2021) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14699 · Cited by 8 · see citing works
Pharmacological manipulation of liver fibrosis progression using novel HDAC 6 inhibitors
Borrello, M. T., Ružić, D., Paish, H. L., Graham, E., Collins, A., Scott, R., Higginbotham, S., Radović, B., Nelson, G., Bulmer, D. M., et al. (2025) · FEBS Journal · doi:10.1111/febs.70062 · Cited by 7 · see citing works
Self-citationJessel, M.-D., McGreevy, O., McReynolds, L., Dahal, L. N., Gilbert, T. M., Malik, H., Goldring, C. E., & Randle, L. E. (2025) · Clinical & Translational Immunology · doi:10.1002/cti2.70057 · Cited by 6 · see citing works
EASL position paper on preclinical models of steatotic liver disease
Gallage, S., Castro, R. E., Estall, J. L., Tabas, I. A., Anstee, Q. M., TINIAKOS, D. G., Szabó, G., Yu, J., Desdouets, C., Tacke, F., et al. (2026) · Journal of Hepatology · doi:10.1016/j.jhep.2026.04.029 · Cited by 6 · see citing works
Self-citationPrecision-cut liver slices as an ex vivo model to assess impaired hepatic glucose production
Kiyuna, L. A., Krishnamurthy, K. A., Homan, E., Langelaar‐Makkinje, M., Gerding, A., Bos, T., Oosterhuis, D., Overduin, R. J., Schreuder, A. B., de Meijer, V. E., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-07070-z · Cited by 6 · see citing works
Ramesh, S., Rao, J. S., Namsrai, B., Fisher, B., Tobolt, D. K., Megaly, M. G., Etheridge, M. L., Pruett, T. L., Seelig, D. M., Murugan, P. J., et al. (2025) · Bioengineering & Translational Medicine · doi:10.1002/btm2.70045 · Cited by 5 · see citing works
Duan, X., Li, S., Li, Q., Wen, W., Mezzetti, O., Warner, C., Xu, M., Jeyarajan, A. J., Li, Y., Shi, Y., et al. (2025) · Hepatology · doi:10.1097/hep.0000000000001597 · Cited by 5 · see citing works
Precision-cut tumor slices for modeling hepatocellular carcinoma enable at-scale drug screening
Collins, A., Kirkness, K., Ramon‐Gil, E., Tzortzopoulou, E., Geh, D., Dishington, J., Graham, E., Muir, R., Cameron, R. I. T., Luli, S., et al. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000706 · Cited by 5 · see citing works
Self-citationJordan, M., Schmidt, K., Fuchs, M., Just, A., Pfanne, A., Willmer, L., Neubert, L., Werlein, C., Zardo, P., Pich, A., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1534989 · Cited by 5 · see citing works
Tavabie, O. D., Salehi, S., & Aluvihare, V. R. (2024) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2024.2331598 · Cited by 5 · see citing works
Prasad, K., Bhattacharya, D., Shams, S. G. E., Izarraras, K., Hart, T., Mayfield, B., Blaszczyk, M. B., Zhou, Z., Pajvani, U. B., Friedman, S. L., et al. (2024) · Cells · doi:10.3390/cells13191651 · Cited by 4 · see citing works
The importance of preclinical models in cholangiocarcinoma
McGreevy, O., Bosakhar, M., Gilbert, T. M., Quinn, M., Fenwick, S. W., Malik, H., Goldring, C. E., & Randle, L. E. (2024) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2024.108304 · Cited by 4 · see citing works
UCHL1-dependent control of hypoxia-inducible factor transcriptional activity during liver fibrosis
Collins, A., Scott, R., Wilson, C. L., Abbate, G., Ecclestone, G. B., Albanese, A., Biddles, D., White, S. A., French, J., Moir, J. A. G., et al. (2024) · Bioscience Reports · doi:10.1042/bsr20232147 · Cited by 4 · see citing works
Self-citationBorthwick, L. A., & Oakley, F. (2019) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2019.10.003 · Cited by 4 · see citing works
Self-citationEvaluation of Gremlin-1 as a therapeutic target in metabolic dysfunction-associated steatohepatitisPreprint
Horn, P., Norlin, J., Almholt, K., Viuff, B. M., Galsgaard, E. D., Hald, A., Zosel, F., Demuth, H., Poulsen, S., Nørby, P. L., et al. (2024) · eLife · doi:10.7554/elife.95185 · Cited by 4 · see citing works
Gallego‐Durán, R., Albillos, A., Ampuero, J., Arechederra, M., Bañares, R., Blas‐García, A., Berná, G., Caparrós, E., Delgado, T. C., Falcón‐Pérez, J. M., et al. (2022) · Gastroenterología y Hepatología (English Edition) · doi:10.1016/j.gastre.2022.02.004 · Cited by 3 · see citing works
Evaluation of Gremlin-1 as a therapeutic target in metabolic dysfunction-associated steatohepatitis
Horn, P., Norlin, J., Almholt, K., Viuff, B. M., Galsgaard, E. D., Hald, A., Zosel, F., Demuth, H., Poulsen, S., Nørby, P. L., et al. (2024) · eLife · doi:10.7554/elife.95185.2 · Cited by 3 · see citing works
Gopireddy, R. R., Bhattacharya, D., Sen, S., Schwartz, M. A., Friedman, S. L., Yu, R. C., Takeuchi, T., & Schwimmer, L. J. (2026) · Molecular Pharmacology · doi:10.1016/j.molpha.2026.100102 · Cited by 3 · see citing works
Mouse Models for the Study of Liver Fibrosis Regression In Vivo and Ex Vivo
Schönke, M., & Rensen, P. C. N. (2024) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2024.00212 · Cited by 3 · see citing works
Putman, M. S., Hull-Meichle, R. L., Waters, S. A., Tuggle, K. L., Sommer, P., Conway, R., Borthwick, L. A., Knudsen, J. G., Dean, E. D., Stanley, S. A., et al. (2026) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2026.03.021 · Cited by 2 · see citing works
Self-citationMeasures of Food Intake, Body Weight Gain, and Energy Efficiency in Mice
Ballard, C. R., & Cazarin, C. B. B. (2022) · Methods and protocols in food science · doi:10.1007/978-1-0716-2345-9_2 · Cited by 2 · see citing works
Hong, J. G., Trotman, J. C., Carbajal, Y., Dey, P., Glass, M., Sclar, V., Alter, I. L., Zhang, P., Wang, L., Chen, L., et al. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000671 · Cited by 5 · see citing works
A Preclinical Model of Human Liver Using Precision Cut Tissue Slice Culture
McGreevy, O., Gilbert, T. M., Jessel, M.-D., Bosakhar, M., Fenwick, S., Malik, H., Goldring, C. E., & Randle, L. E. (2025) · F1000Research · doi:10.12688/f1000research.162495.1 · Cited by 2 · see citing works
Precision-Cut Liver Slices: A Valuable Preclinical Tool for Translational Research in Liver Fibrosis
Perramón, M., Macías-Herranz, M., García-Pérez, R., Jiménez, W., & Fernández-Varo, G. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26167780 · Cited by 3 · see citing works
Vissers, G., Peek, R., Verdurmen, W. P. R., & Nap, A. W. (2024) · Human Reproduction · doi:10.1093/humrep/deae164 · Cited by 2 · see citing works
Mik, P., Barannikava, K., & Surkova, P. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12155072 · Cited by 1 · see citing works
Feng, H., Esposito, C., Benjak, A., Matter, M. S., Cieri, M., Carlo, C. D., Sedlaczek, P., Haak, F., Marinucci, M., Hess, G. F., et al. (2026) · Advanced Science · doi:10.1002/advs.202523976 · Cited by 1 · see citing works
Andrés‐Rozas, M., Aristu-Zabalza, P., Chullo, G., Liu, G., Fundora, Y., Villa, R., Lopez, J., Folguera, C., Fernández‐Iglesias, A., Guixé‐Muntet, S., et al. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119711 · Cited by 1 · see citing works
Zaki, M. Y. W., Shetty, S., Wilkinson, A. L., Patten, D. A., Oakley, F., & Reeves, H. L. (2021) · Journal of Visualized Experiments · doi:10.3791/62868-v · Cited by 1 · see citing works
Self-citationTargeting the αv Integrins in Fibroproliferative Disease
Nanthakumar, C. B., Hatley, R. J. D., & Slack, R. J. (2020) · Royal Society of Chemistry eBooks · doi:10.1039/9781788015783-00037 · Cited by 1 · see citing works
TISSUE ENGINEERING BIOREACTORS: POTENTIAL APPLICATIONS AND SCALE UP STRATEGY
Aladağ, S., & Yapar, E. A. (2020) · Universal Journal of Pharmaceutical Research · doi:10.22270/ujpr.v5i3.416 · Cited by 1 · see citing works
Rudman, J., Marriott, H. M., Carlin, L. M., & Johnston, S. A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/679274
Bhattacharya, D., Becker, C., Readhead, B. P., Goossens, N., Buros, J. L., Fiel, M. I., Cousens, L. P., Magnusson, B., Backmark, A., Hicks, R., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-386482/v1
Zeybel, M., & Mann, D. A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.00262-5
Self-citationUCHL1-dependent control of Hypoxia-Inducible Factor Transcriptional Activity in Liver DiseasePreprint
Collins, A., Scott, R., Wilson, C. L., Abbate, G., Ecclestone, G. B., Biddles, D., Oakley, F., Mann, J., Mann, D. A., & Kenneth, N. S. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.08.523142
Self-citationEvaluation of Gremlin-1 as a therapeutic target in metabolic dysfunction-associated steatohepatitisPreprint
Horn, P., Norlin, J., Almholt, K., Viuff, B. M., Galsgaard, E. D., Hald, A., Zosel, F., Demuth, H., Poulsen, S., Nørby, P. L., et al. (2024) · eLife · doi:10.7554/elife.95185.1
Collins, A., Kirkness, K., Ramon‐Gil, E., Tzortzopoulou, E., Geh, D., Cameron, R., Luli, S., Khurram, E., Storey, D., Paish, H. L., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.16.613213
Self-citationReply to: “Unraveling sphingolipid complexity in liver fibrosis: Perspectives for future research”
Gruevska, A., Oakley, F., & Hall, Z. (2025) · Metabolism · doi:10.1016/j.metabol.2025.156268
Self-citationSaponara, I., Cofano, M., Nunzio, V. D., Bianco, G., Armentano, R., Pinto, G., Caruso, E. A., Centonze, M., & Notarnicola, M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27020594
- Authors
- Paish, H. L., Reed, L. H., Brown, H., Bryan, M. C., Govaere, O., Leslie, J., Barksby, B. S., Garcia Macia, M., Watson, A., Xu, X., Zaki, M. Y. W., Greaves, L., Whitehall, J., French, J., White, S. A., Manas, D. M., Robinson, S. M., Spoletini, G., Griffiths, C., Mann, D. A., Borthwick, L. A., Drinnan, M. J., Mann, J., & Oakley, F.
- Affiliations
- Newcastle University (GB)
- Newcastle Fibrosis Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences,Newcastle University,Newcastle upon Tyne,United Kingdom
- Wellcome Centre for Mitochondrial Research (GB)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Corresponding author
- Oakley, Fiona
- ORCID
- Paish, Hannah L.
- Reed, Lee H.
- Brown, Helen
- Govaere, Olivier
- Leslie, Jack
- Watson, Abigail
- Xu, Xin
- Zaki, Marco Y.W.
- Greaves, Laura
- Whitehall, Julia
- French, Jeremy
- White, Steven A.
- Manas, Derek M.
- Robinson, Stuart M.
- Spoletini, Gabriele
- Griffiths, Clive
- Mann, Derek A.
- Borthwick, Lee A.
- Drinnan, Michael J.
- Mann, Jelena
- Oakley, Fiona
- Venue
- Hepatology
- Published
- 2019-05-28
- Volume
- 70
- Issue
- 4
- Pages
- 1377-1391
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC6852483
- OpenAlex
- W2804042123
- Cited by
- 106
- References
- 33
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 20 · 2023: 10 · 2022: 12 · 2021: 20 · 2020: 12 · 2019: 7
- FWCI
- 8.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Hepatology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- TeesRep (Teesside University) (publishedVersion, cc-by)
- Lirias (KU Leuven) (submittedVersion, cc-by)
- Teesside University Research Portal (Teesside University) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (203105, 203105/Z/16/Z)
- Cancer Research UK (26813, 23390, A23390, C18342/A23390)
- National Institute for Health and Care Research (203105/Z/16/Z)
- Newcastle University (203105/Z/16/Z, L016354)
- European Commission (634413, HORIZON2020)
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000748/1)
- Directorate for Biological Sciences
- SmithKline Beecham Pharma
- AbbVie Biotherapeutics
- Medical Research Council (MR/R023026/1, 203105/Z/16/Z, MR/L016354/1, MC_PC_13071, MK/K001949/1, MC_PC_14101, L016354/1, L016354)
- Engineering and Physical Sciences Research Council (L016354/1, 634413)
- Biotechnology and Biological Sciences Research Council (L016354)
- Economic and Social Research Council (L016354/1)
- NIHR Newcastle Biomedical Research Centre (634413)
- Wellcome Trust Centre for Mitochondrial Research (203105, 203105/Z/16/Z)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- precision-cut liver slices, liver fibrosis, bioreactor cultivation, fibrogenesis, TGF-β1, antifibrotic therapy, nintedanib, obeticholic acid, ALK5 inhibitor, hepatic myofibroblasts, extracellular matrix, albumin secretion, tissue viability
- MeSH terms
- Animals, Biopsy, Needle, Disease Models, Animal, Gene Expression Regulation, Humans, Immunohistochemistry, Liver Cirrhosis, Male, Random Allocation, Sensitivity and Specificity, Time Factors, Rats, Sprague-Dawley, Coculture Techniques, Bioreactors, Tissue Culture Techniques, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
