Pluripotent Stem Cells in Developmental Toxicity Testing: A Review of Methodological Advances

Millions of children are born each year with a birth defect. Many of these defects are caused by environmental factors, although the underlying etiology is often unknown. In vivo mammalian models are frequently used to determine if a chemical poses a risk to the developing fetus. However, there are over 80 000 chemicals registered for use in the United States, many of which have undergone little safety testing, necessitating the need for higher-throughput methods to assess developmental toxicity. Pluripotent stem cells (PSCs) are an ideal in vitro model to investigate developmental toxicity as they possess the capacity to differentiate into nearly any cell type in the human body. Indeed, a burst of research has occurred in the field of stem cell toxicology over the past decade, which has resulted in numerous methodological advances that utilize both mouse and human PSCs, as well as cutting-edge technology in the fields of metabolomics, transcriptomics, transgenics, and high-throughput imaging. Here, we review the wide array of approaches used to detect developmental toxicants, suggest areas for further research, and highlight critical aspects of stem cell biology that should be considered when utilizing PSCs in developmental toxicity testing.