Idiosyncratic drug-induced liver injury (DILI) is a rare adverse drug reaction resulting in liver injury, and a cause of failure in both clinical and post-approval stages of drug development. Predictive the toxicity of new chemicals entities (NCE) is a key challenge to the pharmaceutical industry (FDA, 2009). In order to avoid the use of laboratory animals, and to reduce the cost of pre clinical studies, in vitro toxicology combined the use of cellular models with the measurements of several cell health endpoints in order to predict the hepatotoxicity of NCE. Primary Human Hepatocytes and heptocyte-like cell lines such as HepaRG, Upcytes and HepG2 are commonly used in NCE safety assessment. However, standard cellular assays have shown their limitation to specifically predict DILI potential of NCE (Sison-Young et al., 2017). The era of high content analysis, and especially phenotypic screening, bring new strategy for toxicologist to predict DILIs and their underlying mechanisms, and provides an effective means to reduce drug development failures due to insufficient safety (Xu, 2015).

HCS Pharma is daily developing new cellular assay based on phenotype characterization for toxicology. See our website for more information and feel free to contact us !

Bibliography

This year, the ESTIV (European Society of Toxicology In Vitro) congress took place at Juan-les-Pins, from October 17 to October 20, and was about In Vitro Toxicology for Human Safety Assessment.

It has been a very fruitfull event regarding both the scientific content and the networking possibilities.  Very intense and complete sessions about state of the art regarding in vitro toxicology models and toxicology science were held for the 4 days of the event.

Among all the very good and informative presentations, we were really glad to attend the ones done by collaborators HCS Pharma work with. Also, a poster, showing the results obtained from a collaborative work between HCS Pharma and Galderma, has been presented and discussed with visitors interested in genotoxicity assessment. This poster, about assessment of primary DNA damages with gammaH2AX and comet assays on primary human keratinocytes,  is now accessible on demand !

keratinocyte2

We thank all the scientists we met, either those with whom HCS Pharma already collaborate, the ones with whom we have personnaly worked in the past, and those with whom we had interesting discussions !

To conclude, an aphorism from George Box, dated back to the 70’s, has been cited many times : “All models are wrong, but some are useful.” Among the described futur useful models, many involved 3D culture methods, microfluidics and/or co-culture, with cell lines or stem cells, to better mimic the in vivo situation. Very nice developments were shown, among others, about liver and neuronal models. It strengthens the direction HCS Pharma has taken, as we already have an expanding expertise in these fields.

We are very happy to present you Pierre-Jean Ferron, who joined HCS Pharma as a study director, specialized in cellular biology and high content analysis.

After a master degree in cellular biology and cellular toxicology at Rennes University, Pierre-Jean realized a Ph.D at the Frenh Agency for Food and Safety. During his Ph.D Pierre-Jean has developped high content toxicology assay, based on the use of pertinent cell lines models to study human cytotoxicity of phycotoxins. He then began a post doc in collaboration with the French Institute for Agricultural Research where he studied the toxicological impact of meat contaminants on human cells. For those years, Pierre-Jean has developped strong knowledge in cellular biology and high content analysis, and published several scientific papers.

Genetic Engineering & Biotechnology News (GEN) organise a free webinar about HCS ans HCA use in drug toxicity and genotoxicity testing.

High-content analysis (HCA) and high-content screening (HCS) enable imaging of large numbers of cellular samples for a variety of life science applications. Using automated high-resolution microscopy coupled with analytical software to visualize and quantify phenotypic responses in cells, HCS determines how compounds such as small molecule drugs, antibodies, or siRNA, affect cell morphology in a rapid, quantitative, high-throughput manner, providing meaningful functional readouts of cellular activity.

The broadcast date is Wednesday, June 11, 2014 at 10:00 am ET, 7:00 am PT, 4:00 pm CEST.

Follow this link to register : http://www.genengnews.com/webinars/high-content-screening-and-analysis-in-cell-based-assays-for-drug-toxicity-and-genotoxicity-tes/229/

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