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Today, it is recognized that medicines will eventually be needed during pregnancy, either due to gestation-related medical conditions or pre-existing diseases. Also, 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, information regarding teratogenic risk in humans is often missing for most of the purchased drugs. Inter-species differences have limited the suitability of animal 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.

Mariana Branco, a PhD candidate at the Stem Cell Engineering Research Group of iBB (SCERG-iBB), was awarded with the prize of best oral presentation at the 11th International Meeting of the Portuguese Society for Stem Cells and Cell Therapies (SPCE-TC) that was held during the last 11 – 13th of October at Faculdade de Farmácia of Universidade de Lisboa. The oral communication was entitled “Transcriptomic analysis of 3D cardiac differentiation of human induced pluripotent stem cells reveals faster maturation of cardiomyocytes compared to 2D culture”. Congratulations Mariana!

The embryonic development of the human heart under healthy and pathological conditions is still very poorly understood. In a recently published Nature Communications paper, a iBB team led by Margarida Diogo, in collaboration with Perpetua Pinto do Ó at i3S, engineered a unique organ-like model from stem cells that recreates several stages of embryonic development of the human heart. This humanized model opens now the path to study, in a tissue engineering lab, the development of congenital heart diseases, such as coronary vascular diseases and myocardium non-compaction cardiomyopathies, and can be further applied in drug screening and toxicology assays during embryonic heart development. This last topic is particularly relevant since pregnant women normally do not take part in clinical trials, making this human cell-based in vitro platform the only viable alternative to assess developmental cardiotoxicity. The work was a part of the PhD thesis in Bioengineering – MIT Portugal program of Mariana Branco, the first author of the paper, and was funded by the FCT project “Mini-Hearts - Organoid Engineering for Production of 3D Cardiovascular Microtissues from Human Induced Pluripotent Stem Cells for Cardiotoxicity”.