|Cells||Embryonic stem cells bearing a read-out system for cardiac differentiation|
|Reporter||TAQ GFP or SEAP|
|Service Content||Comparative investigation of embryotoxicity and/or teratogenicity and cytotoxcity of test compounds on differentiating mouse ESC.|
|Delivery||A study protocol will be sent to initiate the study. Results are sent as draft and final study report.|
|Timelines||Experiment time: 4 weeks per compound.
Draft report: within 8 weeks
The µEST@ test system utilises the ability of mouse embryonic stem cells (ES cells) to differentiate in vitro into various tissues of all three germ layers. Supposing that exposure of ES cells to embryotoxic and teratogenic compounds during this process interferes with correct differentiation, the resulting amount of a given tissue, e.g. cardiac tissue, will be a marker for developmental toxicity. To distinguish a specific embryotoxic effect from a plain cytotoxic effect, results of the µEST@ are compared to results from a standard cytotoxicity assay (XTT test).
The mechanistic principle of the test was described by Spielmann et al. in 1997 and validated by the ECVAM Scientific Advisory Committee (ESAC) in 2001. The µEST@ test system was stated equivalent to the validated EST by ECVAM, and gained acceptance as "suitable for REACH" by ECVAM in 2008.
Predictivity of µEST@ (70 compounds tested within the ECVAM validation studies)
- Specificity 87%
- Sensitivity 88%
- Negative predictive value 81%
- Positive predictive value 91%
- Accuracy 87%