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 Around 85% of drugs are ultimately withdrawn from the market when this biotransformation causes hepatotoxicity.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)

Competitive advantages

  • 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

VUB TechTransfer
Hugo Loosvelt
[T]: +32 (0)2 629 38 65 or 22 07
[E]: hugo.loosvelt@vub.ac.be

In Vitro Toxicology and Dermato-cosmetology (IVTD)
Vera Rogiers
[T]: +32 (0)2 47745 16
[E]: vera.rogiers@vub.ac.be
Ruani Fernando
[T]: +32 (0)2 47745 20
[E]: ruani.fernando@vub.ac.be

Patent details

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.