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 : Microarray analysis revealed that HDV but not HBV infection activated a broad range of interferon stimulated genes (ISGs) in HepG2NTCP cells. HDV strongly activated IFN-β and IFN-λ in cell lines and PHH. HDV induced IFN levels remained unaltered upon RIG-I or TLR3 knock-down, but were almost completely abolished upon MDA5 depletion. Conversely, overexpression of MDA5 but not RIG-I and TLR3 in Huh7.5NTCP cells partially restored ISG induction. During long-term infection, IFN levels gradually diminished in both HepG2NTCPand HepaRGNTCP cell lines. MDA5 depletion had little effect on HDV replication despite dampening HDV-induced IFN response. Moreover, treatment with type I or type III IFNs did not abolish HDV replication.
Abstract : Pyrrolizidine alkaloids (PA) are secondary plant compounds. PA intoxication in humans causes severe acute and chronic hepatotoxicity. However, the molecular mechanisms of PA hepatotoxicity in humans are not well understood yet. Therefore, we investigated cell death parameters in human HepaRG cells following either single (24?h) or repeated dose treatment (14?d) with structurally different PA of the retronecine (echimidine, senecionine), heliotridine (heliotrine), and otonecine type (senkirkine). After 24?h of exposure only retronecine-type PA were cytotoxic in HepaRG cells and induced apoptosis indicated by a loss of membrane asymmetry, disruption of the mitochondrial membrane potential, and increased pro-caspase and PARP cleavage. In contrast, after 14?d all four PA exerted the aforementioned effects. Furthermore, the apoptotic events caspase 3, 8 and 9 activation as well as nuclear condensation and DNA fragmentation were only detected for the retronecine-type PA after single exposure (6?h). Overall, our studies revealed a time- and structure-dependent apoptosis after PA exposure, suggesting that retronecine-type PA seem to be more potent apoptosis inducers than heliotridine- or otonecine-type PA. Furthermore, our results suggest that PA-induced apoptosis in HepaRG cells occur most probably by involving both, the extrinsic death receptor pathway as well as the intrinsic mitochondrial pathway.
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.