Embryonic Stem cell-based Novel Alternative Testing Strategies (ESNATS)

04/2008-09/2013

This third-party funded project is conducted in the framework of the BfR research program for alternatives to animal experiments.

Support code of the EU: HEALTH-F5-2008-201619

Homepage of the project: -

ESNATS aimed at developing a novel toxicity test platform based on embryonic stem cells (ESCs), in particular human ESC (hESCs), to accelerate drug development, reduce R&D costs and propose a powerful alternative to animal tests in the spirit of the "Three R Principle".

ESNATS addressed current shortcomings in drug toxicity testing:

• testing takes place late in the development cycle, implying use of high numbers of animals and generating significant costs,
• animal-based test systems bear the risk of non-prediction due to inter-species variation,
• in vitro assays rely on primary cells or cells lines of malignant origin that are hard to standardize 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 of cells in native tissue.

To overcome these shortcomings, ESNATS developed a novel testing system taking advantage of the unique potential of ESCs, including:

• their capacity to self-renew, constituting an unlimited source of standardized cells,
• their pluripotency, providing a source for cells of different phenotypes required for toxicity testing,
• the physiological relevance of ESC-derived somatic cells for toxicity endpoints, guaranteeing high test predictivity,

at least for murine ESC (mESC), their easy genetic manipulation, allowing use of reporter gene expression as a powerful toxicity testing tool.