Embryonic stem cells in safety pharmacology and toxicology.

Embryonic stem (ES) cells undergo self-renewal and are pluripotent, i.e., they can give rise to all the types of specialised cells in the body. Scientific knowledge on ES cells is increasing rapidly, leading to opportunities for establishment of ES cell-based in vitro tests for drug discovery, preclinical safety pharmacology and toxicology. The main properties of ES cells making them useful in in vitro assays are that they have a normal diploid karyotype and can provide a large number of cells for high-throughput assays. Human ES cells additionally have the potential to provide solutions to problems related to interspecies differences and methods for screening for human polymorphisms, thus supporting robust human hazard identification and optimised drug discovery strategies. Importantly, ES cell based assays could be potential tools to reduce and perhaps replace, animal experiments. This chapter will describe ongoing research in the use of ES cells in toxicology and safety pharmacology, focusing on the major areas of progress, namely, embryotoxicology, cardiotoxicology and hepatoxicology.