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ESNATS aims at developing a novel toxicity test platform based on embryonic stem cells (ESC), especially human ESC (hESC), to accelerate drug development, reduce R&D costs and propose a powerful alternative to animal tests (3 Rs). ESNATS will address current drug-testing shortcomings: - testing takes place late in the development cycle - animal test systems bear the risk of non-prediction due to inter-species variation - non-ESC assays rely on primary cells or cells of malignant origin that are hard-to-standardise and limited in regard to quantity, homogeneity and genetic diversity - existing assay systems based on primary animal cell lines do not reliably represent the physiological situation ESNATS will develop a battery of toxicity tests using hESC lines subjected to different standardised culture protocols. Tests will cover embryoid bodies in different developmental stages and differentiated derivatives including gamete and neuronal lineages, complemented with test systems for hepatic metabolism. Predictive toxicogenomics and proteomics markers will be identified. The individual tests will be integrated into an "all-in-one" test system. To enable future industrial use ESNATS will prepare automating and scaling up of hESC culture. The predictivity, quality and reproducibility of ESNATS will be evaluated in a proof of concept study. ESNATS benefits are to increase safety due to better predictivity of human test systems, to reduce, refine and replace animal tests, to lower testing cost, and to support medium/high throughput testing. ESNATS objectives will be achieved in a 5 year multi-disciplinary collaboration of leading European researchers in alternative testing, toxicology, ESC research, genomics, modelling, and automation. The consortium will also include representatives from regulatory bodies, the pharmaceutical industry and ethical advisors to provide guidance to ensure rapid applicability of the developed tests systems. |
