Stem Cells in Developmental Toxicity Testing

In the last several years, a great deal of research has revolved around the refinement of existing alternative tests for developmental toxicity and the development of assays to monitor different endpoints. Differentiation of mouse embryonic stem cells has been used to test the developmental toxicity of a number of compounds. The original test, as validated by the European Center for the Validation of Alternative Methods, was able to correctly categorize 78% of tested chemicals (Genschow et al., 2002). However, refinements and additions to the assay were suggested to increase prediction accuracy. Those suggestions included additional endpoints to evaluate tissues derived from other germ cell layers, more quantifiable endpoints, shorter assay times, and more high-throughput tests. Examples of assays that have addressed each of those concerns are included in this review. Much less work has been done to develop assays to predict developmental toxicity that use human cells. Although the availability of human induced pluripotent stem cells has spurred the development of assays for toxicity testing of other endpoints (e.g., cardiotoxicity), relatively few publications have focused on the use of these cells for developmental toxicity testing. This may be in part because of the difficulty in culturing and differentiating human cells. Examples of some of the assays that have been developed using human cells are also included in this review.