SAY HELLO AT EUROTOX
CURRENT INTERESTS AND UNDERSTANDING
There is currently interest in the construction of complex in vitro models with the eventual goal of simulating the behaviour of an organ or even a whole organism. Our gold standard for clinical response is the human body. It is now recognised that 3D cell cultures are more representative of human physiology than 2D monolayers of cells growing on a flat surface. Correct organ function also requires gradients of oxygen and metabolites and removal of waste material, as well as co-culture of multiple cell type.
MIMICKING CLINICAL BEHAVIOUR
To accurately mimic clinical behaviour, cells should be in a 3D environment and provided with a physiologically-relevant flow of media. Past workers have shown that primary hepatocytes cultured in a collagen sandwich show more human-like expression of key detox genes (Vinci et al. 2011) and fibroblasts cultured under flow show vastly different gene expression profiles compare with those cultured in static conditions (Nithiananthan et al. 2016).
EVIDENCE FOR FLOW
We show that flow conditions significantly upregulate phase I and phase II metabolic enzyme genes in a 3D culture and this is reflected in the metabolism of certain tested drugs. In line with the mRNA data, CYP2D6 (dextromethorphan) was not influenced by flow, but both phase I and II metabolism of Midazolam (CYP3A4 and UGT) were strongly upregulated. When challenged by diclofenac for up to 24 hours, primary rat hepatocytes give a more realistic assessment of toxicity. The Quasi Vivo® system is also 50% more accurate in predicting the IC50 for APAP and cyclophosphamide.
MEET WITH KIRKSTALL
If you are attending Eurotox, or know someone who is, we’d very much appreciate the opportunity to discuss your research and how adding fluid flow might be of great benefit;
POSTER PRESENTATION INFORMATION:
- Abstract Title: Improved IC-50 prediction using the Quasi Vivo &[reg] in vitro dynamic cell culture flow system
- Authors: Dr John Malcolm Wilkinson, Dr Kelly Davidge
- Poster Session: 5
- Theme: Target Organ toxicity, Liver
- Type of poster: E-poster and printed poster
- Poster board Number: P-12-00-10
- Poster Manning Time: Wednesday, September 13, 09:30–10:00
- Location: Slovak National Theatre
Would you like to set up a meeting with Malcolm in Bratislava?
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