Multilevel in vitro platform for liver toxicity screening
The liver is the most important site of drug metabolism in the body, with approximately 60% of marketed compounds being cleared by hepatic biotransformation. However some drugs undergo metabolic bioactivation producing harmful metabolites. Around 85% of drugs are ultimately withdrawn from the market when this biotransformation causes hepatotoxicity. Consequently the evaluation of drug metabolism and drug-mediated responses is an essential step in the development of new pharmaceuticals.
Solution: fully-customised multilevel panel of cellular assays
Based on more than 30 years experience in the field of liver in vitro modelling, the In Vitro Toxicology and Dermato-cosmetology (IVTD) research group of the VUB offers a fully-customised multilevel panel of cellular assays (see figure), ranging from large-scale, short-term testing in basic in vitro hepatocyte models to long-term in-depth studies employing state of the art hepatic cell systems, such as proprietary human stem cell-derived hepatic cells* or cell lines, e.g. HepaRG™. Species-specificity of hepatic metabolism can be taken into account by inclusion of both, animal- and human-derived cell models. Upon exposure to the test compound of interest, a variety of cell functions can be examined including:
- proliferation: DNA synthesis, cell cycle markers
- functional status: albumin and urea production, phase I cytochrome P450- mediated metabolism, phase II metabolism, influx transporters and biliary excretion stress and cytotoxic responses: oxidative stress, cytotoxicity (necrotic and apoptotic cell death), genotoxicity, steatosis, phospholipidosis, cholestasis
- cellular readouts: including mRNA (RNA sequencing, DNA microarrays, RTqPCR), protein (western blot, ELISA, immunohistochemistry, FACs) and activity (diverse colorimetric and fluorometric assays)
- access to state of the art hepatocyte models, including proprietary stem cell-derived hepatic cells (EP1824965 B1)*
- access to animal models of liver injury
- expertise in highly optimised protocols including, in-house microarray platform and software for toxicogenomic/transcriptomic studies
- access to over 200 hepatocyte-specific markers (PCR primers)
*See also tech offer 'Human stem cell-based platform for the early detection of drug-induced liver injury (DILI).
Valuable for the early detection of drug-induced liver injury (DILI) towards safety testing in:
- the cosmetic industry
- the pharmaceutical industry
- the chemical industry
Interested parties can contact
[T]: +32 (0)2 629 38 65 or 22 07
Granted patent application EP1824965 (B1), titled “Differentiation of stem cells and stabilization of phenotypical properties of primary cells”, validated and maintained in UK, Germany and France.
Download a printable pdf here.