Stem cells and tissue engineering technologies for advancing human teratogen screening

This chapter will cover the use of stem cells and tissue engineering technologies in the assessment of developmental and reproductive toxicity (DART). We will first give an overview of current animal-based DART regulatory guidelines to highlight opportunities where in vitro assays can replace or complement animal testing in the identification of potential teratogens. To date, animal embryo-based in vitro assays, such as rat whole embryo culture (WEC), zebrafish and chicken embryo models, have been explored as animal alternatives for teratogen testing. We will briefly summarize salient features of these in vitro embryo culture systems and discuss recent technological advances, such as the use of microfluidic platforms to facilitate improvements in assay robustness and throughput. More recently, pluripotent stem-cell (PSC)-based assays for teratogen screening are increasingly being developed because they can potentially be human-specific via the use of human PSCs. Moreover, PSC-based models allow one to probe and measure teratogenic effects through multiple readouts, including changes in molecular biomarker expression, metabolite profiles, as well as cellular differentiation and migration phenotypes. The adoption of tissue engineering approaches to control PSC differentiation rates into various tissue types will allow for more realistic modeling of embryonic developmental processes to screen for potential teratogens with higher throughput and precision.