In-vitro toxicity testing applications: Hepatotoxicity (reactive metabolites, lipidosis, choleastasis etc), Virology (HBV, HCV…), Infection with hepatitis and other viruses for replication, ...
Liver assist devices/ BioArtificial Livers
Transgenic liver humanized animals with HepaRG™ cells
…. an ever-expanding range of applications!
HeparRG™ cells are more economical, convenient, and predictable than fresh or cryopreserved primary human hepatocytes. It's available in proliferative state to be expanded and differentiatedin-house, or as cryopreserved, fully differentiated and ready-to-use hepatic cells.
Full array of functions, responses, and regulatory pathways of primary human hepatocytes including:Phase I and II, and transporter activities consistent with those found within a population of primary human hepatocytes + Intact response elements, PXR, CAR and PPARa
Form bile canaculi
Has the potential to express major properties of stem cells
High plasticity & complete transdifferentiation capacity
Abstract : Hepatic steatosis (i.e. lipid accumulation) and steatohepatitis have been related to diverse etiologic factors, including alcohol, obesity, environmental pollutants. However, no study has so far analyzed how these different factors might interplay regarding the progression of liver diseases. The impact of the co-exposure to the environmental carcinogen benzo[a]pyrene (B[a]P) and the lifestyle-related hepatotoxicant ethanol, was thus tested on in vitro models of steatosis (human HepaRG cell line; hybrid human/rat WIF-B9 cell line), and on an in vivo model (obese zebrafish larvae). Steatosis was induced prior to chronic treatments (14, 5 or 7 days for HepaRG, WIF-B9 or zebrafish, respectively). Toxicity and inflammation were analyzed in all models; the impact of steatosis and ethanol towards B[a]P metabolism was studied in HepaRGcells. Cytotoxicity and expression of inflammation markers upon co-exposure were increased in all steatotic models, compared to non steatotic counterparts. A change of B[a]P metabolism with a decrease in detoxification was detected in HepaRG cells under these conditions. A prior steatosis therefore enhanced the toxicity of B[a]P/ethanol co-exposure in vitro and in vivo; such a co-exposure might favor the appearance of a steatohepatitis-like state, with the development of inflammation. These deleterious effects could be partly explained by B[a]P metabolism alterations.
Abstract : Drug-induced liver injury is one of the main causes of drug non-approval and drug withdrawal by the Food and Drug Administration (FDA). Bavachinin (BVC) is a natural product derived from the fruit of the traditional Chinese herb Fructus Psoraleae (FP). There have been reports of acute liver injury following the administration of FP and its related proprietary medicines. To explore BVC hepatotoxicity and its mechanisms, we used the HepaRG cell line. In our recent research, we showed that BVC induces HepaRG cell death, mainly via BVC-induced oxidative damage. The formation of ROS is closely related to the activation of the stress-activated kinases, JNK and p38, while SP600125 (SP, JNK inhibitor) and SB203580 (SB, p38 inhibitor) pretreatment inhibited the generation of ROS. On the other hand, N-acetylcysteine (NAC) pretreatment prevented the phosphorylation of p38 but not that of JNK. Taken together, these data reveal that BVC induces HepaRG cell death via ROS and the JNK/p38 signaling pathways.
Time lapse (Total recording time: 2 hours). Chlormoprazine superior to 40µM constricts the bile lumen and provokes cholestasis. Constriction of canaliculus lumen has been observed in presence of CPZ after 2 hours.