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Pluripotent Stem Cells as Tools to Assess Developmental Toxicity: Diversity Instead of Consolidation

Abstract

As pharmaceutical and biotechnology industries develop more potentially toxic compounds, traditional methods of toxicity screening cannot keep up. A conventional approach of screening compounds for their toxic and teratogenic potential heavily relies on multitudes of animal models, which have proven to be timely and expensive and bring forth ethical challenges. These limitations of animal testing have created an eagerness among researchers to develop more predictive in vitro alternative screening assays. The most promising in vitro approach at modernizing toxicity tests is the embryonic stem cell test (EST). The EST assesses toxicity on the naive embryonic cell and also the effect of the putative toxicant on the genesis of a specific tissue endpoint. Importantly, unlike other in vitro models, the EST obviates the need to sacrifice pregnant animals. Although determined suitable for regulatory standards, the classic EST, which is based on mouse cells, is limited in its endpoint analysis and efficient prediction of human response. Those limitations have led to numerous unconsolidated improvements to the assay. This chapter provides an overview of the classic EST as it has been developed in 1997 and illustrates disadvantages of the classic EST as well as the numerous modifications to it.

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