Specific activation of the different fibrogenic cells in rat cultured liver slices mimicking in vivo situations

• Published in: Virchows Archiv : an international journal of pathology 2007-05, Vol.450 (5), p.503-512
• Main Authors: GUYOT, Christelle, COMBE, Chantal, CLOUZEAU-GIRARD, Haude, MORONVALLE-HALLEY, Valérie, DESMOULIERE, Alexis
• Format: Article
• Language: English
• Subjects: Acetaminophen - toxicity; Acetylcysteine - pharmacology; Animal Use Alternatives; Animals; Antioxidants - pharmacology; Bile Ducts, Intrahepatic - drug effects; Bile Ducts, Intrahepatic - pathology; Biological and medical sciences; Cell Survival - drug effects; Disease Models, Animal; Drug Antagonism; Epidermal Growth Factor - pharmacology; Estradiol - pharmacology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatocytes - drug effects; Hepatocytes - pathology; Investigative techniques, diagnostic techniques (general aspects); Kupffer Cells - drug effects; Kupffer Cells - metabolism; Kupffer Cells - pathology; Lesions; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver Cirrhosis - chemically induced; Liver Cirrhosis - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Necrosis; Organ Culture Techniques; Other diseases. Semiology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Portal System - drug effects; Portal System - metabolism; Portal System - pathology; Proteins; Rats; Rats, Wistar; Subpopulations; Thioacetamide - toxicity
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-007-0390-y

Due to the loss of cell-cell and cell-matrix interactions, cell culture models poorly mimic the in vivo situation. Therefore, we tested the applicability of precision-cut liver slices (PCLS) to study the early activation of the two main liver fibrogenic cell subpopulations: hepatic stellate cells (HSC) and portal fibroblasts (PF). PCLS were treated with thioacetamide or acetaminophen to induce HSC activation. In PCLS culture, both were able to trigger centrolobular lesion and HSC activation as observed in vivo. However, thioacetamide also presented a toxic effect on portal tract cells. In this PCLS model of centrolobular lesion, the antioxidant N-acetylcysteine was able to prevent acetaminophen-induced injury. To induce a specific activation of PF, PCLS were treated with epidermal growth factor or beta-oestradiol. As in vivo, epidermal growth factor and beta-oestradiol induced bile duct epithelial cell proliferation accompanied by PF activation; however, beta-oestradiol also triggers sinusoidal cell proliferation. We demonstrated that treatments usually used in vivo to induce liver fibrosis allow, in cultured PCLS, the specific activation of the two main liver fibrogenic cell subpopulations, making this model very useful to study the mechanisms involved in early fibrogenic cell activation.