Chen Xinrong, Hansen Deborah K, Merry Gwenn, DeJarnette Christian, Nolen Greg, Sloper Daniel, Fisher J Edward, Harrouk Wafa, Tassinari Melissa S, Inselman Amy L
Division of Systems Biology, National Center for Toxicological Research, Food and Drug Administration.
Lee University.
Reprod Toxicol. 2015 Jun;53:131-40. doi: 10.1016/j.reprotox.2015.04.008. Epub 2015 Apr 27.
The mouse Embryonic Stem cell Test (EST) using cardiomyocyte differentiation is a promising in vitro assay for detecting potential embryotoxicity; however, the addition of another differentiation endpoint, such as osteoblasts, may improve the predictive value of the test. A number of variables such as culture conditions and starting cell number were investigated. A 14 day direct plating method of D3 mouse embryonic stem cells (mESCs) was used to test the predictivity of osteoblast differentiation as an endpoint in the EST. Twelve compounds were tested using the prediction model developed in the ECVAM validation study. Eight of the compounds selected from the EST validation study served as model compounds; four additional compounds known to produce skeletal defects were also tested. Our results indicate comparable chemical classification between the validated cardiomyocyte endpoint and the osteoblast endpoint. These results suggest that differentiation to osteoblasts may provide confirmatory information in predicting embryotoxicity.
