Developmental Toxicity Studies: The Path towards Humanized 3D Stem Cell-Based Models

Abstract

Today, it is recognized that medicines will eventually be needed during pregnancy to help prevent to, ameliorate or treat an illness, either due to gestation-related medical conditions or pre-existing diseases. Adding to that, the rate of drug prescription to pregnant women has increased over the past few years, in accordance with the increasing trend to postpone childbirth to a later age. However, in spite of these trends, information regarding teratogenic risk in humans is often missing for most of the purchased drugs. So far, animal models have been the gold standard to obtain teratogenic data, but inter-species differences have limited the suitability of those models to predict human-specific outcomes, contributing to misidentified human teratogenicity. Therefore, the development of physiologically relevant in vitro humanized models can be the key to surpassing this limitation. In this context, this review describes the pathway towards the introduction of human pluripotent stem cell-derived models in developmental toxicity studies. Moreover, as an illustration of their relevance, a particular emphasis will be placed on those models that recapitulate two very important early developmental stages, namely gastrulation and cardiac specification.