Pluripotent stem cells for target organ developmental toxicity testing

Prenatal developmental toxicity research focuses on understanding the potential adverse effects of environmental agents, drugs, and chemicals on the development of embryos and fetuses. Traditional methods involve animal testing, but ethical concerns and the need for human-relevant models have prompted the exploration of alternatives. Pluripotent stem cells (PSCs) are versatile cells with the unique ability to differentiate into any cell type, serving as a foundational tool for studying human development. Two-dimensional (2D) PSC models are often chosen for their ease of use and reproducibility for high-throughput screening. However, they lack the complexity of an in vivo environment. Alternatively, three-dimensional (3D) PSC models, such as organoids, offer tissue architecture and intercellular communication more reminiscent of in vivo conditions. However, they are complicated to produce and analyze, usually requiring advanced and expensive techniques. This review discusses recent advances in the use of human PSCs differentiated into brain and heart lineages and emerging tools and methods that can be combined with PSCs to help address important scientific questions in the area of developmental toxicology. These advancements and new approach methods align with the push for more relevant and predictive developmental toxicity assessment, combining innovative techniques with organoid models to advance regulatory decision-making.