Evaluation of cultured, precision-cut rat liver slices as a model to study drug-induced liver apoptosis

Moronvalle-Halley, V.; Sacré-Salem, Béatrice; Sallez, Valérie; Labbe, Gilles; Gautier, Jean‐Charles

doi:10.1016/j.tox.2004.09.014

Cited by 29 publications

(12 citation statements)

References 32 publications

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“…26 Male Wistar rats (Charles Rivers, St Aubin les Elbeuf, France) weighing approximately 400 g were anesthetized with an intraperitoneal injection of ketamine (Imalgen s , Rhô ne Mérieux, Lyon, France) and xylazine (Rompun s , Bayer Pharma, Puteaux, France). Liver was perfused in situ (20 ml/min) with preoxygenated ice-cold Hanks' balanced salt solution (Invitrogen, Cergy Pontoise, France), supplemented with 5 mM glucose and 50 mg/ml gentamycin, via a plastic catheter placed in the portal vein.…”

Section: Preparation Of Rat Pclsmentioning

confidence: 99%

Effects of bile acids on biliary epithelial cell proliferation and portal fibroblast activation using rat liver slices

Clouzeau-Girard

Guyot

Combe

et al. 2006

Laboratory Investigation

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During cholestasis, bile acids accumulate in the liver, and induce cellular alterations. Cholestasis is a major cause of liver fibrosis. We have used precision-cut liver slices (PCLS) in culture to investigate the effects of bile acids on hepatic cells. Rat PCLS were placed on an insert in a vial containing culture medium, and gently agitated on a roller platform. PCLS were treated with 100 lM taurolithocholate (TLC), taurodeoxycholate (TDC) or taurocholate (TC) for 24 or 48 h. PCLS viability was measured, and immunohistochemistry was performed with antibodies against active caspase 3, platelet-derived growth factor (PDGF) receptor-b and ED-A fibronectin. TDC and TLC, two hydrophobic bile acids, induced hepatocyte necrosis and apoptosis, whereas TC, an hydrophilic bile acid, improved slice viability as compared with controls. Both TDC and TC induced biliary epithelial cell proliferation, together with portal fibroblast proliferation and activation, as shown by PDGF receptor-b and ED-A fibronectin expression. TLC induced biliary epithelial cell apoptosis. Our results indicate that individual bile acids induce cell type-specific effects in a complex liver microenvironment. The fact that PCLS support biliary epithelial cell and portal fibroblast proliferation will make this model very useful for the study of the mechanisms involved in portal fibrosis.

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Section: Preparation Of Rat Pclsmentioning

confidence: 99%

Effects of bile acids on biliary epithelial cell proliferation and portal fibroblast activation using rat liver slices

Clouzeau-Girard

Guyot

Combe

et al. 2006

Laboratory Investigation

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“…Cultured liver tissue could be a useful tool for investigating the interaction between and maintenance of cells in a normal histo-architecture. 3,4 The long-term culture of precision-cut liver tissue slices has been employed for many applications. 5,6 It has mainly been used for testing the metabolism and toxicity of chemicals in the liver tissue.…”

Section: Introduction Lmentioning

confidence: 99%

Perfusion Culture Improves the Maintenance of Cultured Liver Tissue Slices

Schumacher

Khong²,

Chang³

et al. 2007

Tissue Engineering

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Cultured precision-cut liver tissue slices are useful for studying the metabolism and toxicity of xenobiotics in liver. They may also be used to investigate the behavior of and interaction between different cell types in an intact histo-architecture. Because cultured liver tissues undergo a loss of function and morphology because of their separation from the blood supply, we investigated changes in key protein marker expressions in parenchymal and non-parenchymal cells, as well as in the extracellular matrix (ECM) at different time points. We also compared conventional culture methods such as static and dynamic cultures with perfusion culture, which allows a continuous exchange of the culture medium. In conventional culture methods, the expression of vimentin and collagen type IV decreased after 5 h in the non-parenchymal cells and the ECM, respectively, whereas the hepatocyte nuclear factor 4 alpha (HNF4a) staining in the hepatocytes remained constant. In perfusion culture, on the other hand, vimentin, collagen type IV, and HNF4a staining were clearly detectable after 5 h. The histo-architecture obtained from perfusion culture was also more compact than those obtained from conventional culture methods. After 24 h, only the perfusion cultured sample retained protein marker expression in all components of the liver tissue. Our results suggest that, to develop improved culture techniques for liver slices, changes at the early time-points should be taken into consideration. Our results also show that culture techniques that enable a continuous exchange of the culture medium seem to be superior to static or dynamic cultures in terms of maintaining the protein expression and the histo-architecture.

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“…Precision-cut liver slices (PCLS) have been used for metabolic and toxicological studies on various liver cell types [7,8]. The PCLS culture model allows the maintenance of normal lobular architecture and of cell-cell interactions within their original matrix.…”

Section: Introductionmentioning

confidence: 99%

Fibrogenic cell fate during fibrotic tissue remodelling observed in rat and human cultured liver slices

Guyot

Combe

Balabaud

et al. 2007

Journal of Hepatology

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Evaluation of cultured, precision-cut rat liver slices as a model to study drug-induced liver apoptosis

Cited by 29 publications

References 32 publications

Effects of bile acids on biliary epithelial cell proliferation and portal fibroblast activation using rat liver slices

Effects of bile acids on biliary epithelial cell proliferation and portal fibroblast activation using rat liver slices

Perfusion Culture Improves the Maintenance of Cultured Liver Tissue Slices

Fibrogenic cell fate during fibrotic tissue remodelling observed in rat and human cultured liver slices

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