As shown by AstraZeneca in nature reviews*, one third of safety failures along the drug discovery process is linked to CNS toxicity uncovered in clinical trials. To avoid this attrition, the potential neurotoxicity of any drug going through the blood brain barrier (BBB) needs to be assessed in the very early stages of new chemical entities (NCE) research. Neurotoxicity assays can be performed on the SH-SY5Y human cell line by using High-Content Screening (HCS) technologies. The present study was performed using classical 2D and 3D culture protocols. In this poster, 2D results and preliminary 3D culture results on multiple reference compounds are depicted.

View and download on Slideshare (low quality) : https://www.slideshare.net/hcspharma/in-vitro-dermocosmetology-high-content-analysis-approach-using-human-primary-keratinocytes-and-fibroblasts

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Cell biology is part of the R&D activity in dermocosmetology, as providers of active extracts or pure compounds have to demonstrate their efficacy and safety. At HCS Pharma, we are developing new dermocosmetology assays on relevant cellular models, like human primary keratinocytes and human primary fibroblasts, using our automated platform and high content analysis system. Through the use of 96 or 384 wells plates combined with process automation, we constantly increase the throughput in order to allow proof of concept assays of one or several compounds up to the screening of large compounds libraries, for single endpoint or live cells analysis to multiplexed phenotypic screening.
Assessment of compounds activity/safety can be performed on several parameters in parallel with a multiplexed assay. Among them, we describe here wound healing, inflammation assay & extra cellular matrix analysis, which are routinely performed. Other parameters can be analysed on demand on live and fixed cells, using chemical probes or immunocytochemistry.

View and download on Slideshare (low quality) : https://www.slideshare.net/hcspharma/in-vitro-dermocosmetology-high-content-analysis-approach-using-human-primary-keratinocytes-and-fibroblasts

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Since few years, the technology is more and more used to finaly create organ-on-a-chip and now body-on-chip with different organs. More and more academical units and collaborative projects allowed to succed to miniaturise different organs in different chambers on a chip connected with microfluidy. Lung, liver, kidney, heart, bone, bone marrow, adipose tissue, intestine, skin, blood vessels, blood-brain barrier are already exist on a chip. But the way is long and some problems are still not resolved as  the use of polydimethylsiloxane (PDMS), which absorbed hydrophobic drugs.

But can we imagine to have all organs of the body on a chip to test the safety of a drug in one in vitro experiment? This was the project of different partnairs and collaborations and one is in France in Compiegne:

“Une équipe française est active dans ce domaine. Basée à l’université de technologie de Compiègne, elle travaille avec le laboratoire franco-japonais LIMMS (CNRS université de Tokyo) à la mise au point d’un foie sur puce. En Europe, cinq partenaires, implantés en Suisse, Belgique, Allemagne et Royaume-Uni, collaborent à un projet de body-on-a-chip qui a reçu de l’UE un financement de 1,4.million d’euros. Une puce comprenant quatre types de cellules (foie, tumeur, muscle cardiaque, tissu nerveux) a été réalisée. Aux États-Unis, le projet de body-on-a-chip du MIT a reçu une subvention de 32 millions de dollars, le Wyss Institute une enveloppe de 37 millions.”

Can we imagine to replace the majority of animal testing and to be more and more predictive during the preclinical phases with all these new technologies (microfluidy, bioprinting,…). And by using cells coming from patients as IPS with using these new technologies, we will slowly but surely towards personalized medicine.

To know more on this project on body on a chip, go to this link (article in french): http://www.sciencesetavenir.fr/sante/e-sante/20151120.OBS9895/organes-artificiels-ces-puces-qui-miment-le-vivant.html

The whole blood cytotoxicity assay (WCA) is a cytotoxicity assay developed by incorporating high-throughput cell positioning technology with fluorescence microscopy and automated image processing. Here, we describe how lymphoma cells treated with an anti-CD20 antibody can be analyzed real-time in human whole blood to provide quantitative cellular cytotoxicity analysis.

Curated from www.jove.com

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