Preclinical assessment of cardiac toxicity.

The exact prediction of the clinical behavior of drugs represents one of the most difficult duties in preclinical drug development. The use of cell-based assay systems underpins the development of many drug candidates, but owing to the artificial character of many of these systems, cell response and physiological behavior seem to be mutually exclusive. Embryonic stem cell-derived cells represent a system that may address the disconnect between the behavior of cultured cells and cells in situ. While undifferentiated ES cells allow standardization, expansion and genetic manipulation, the differentiated cells provide a reflection of the normal physiological image of their primary counterpart. We compare common models to detect cardiac toxicity with an assay system comprising in vitro differentiated pure cardiomyocytes.