Advanced human developmental toxicity and teratogenicity assessment using human organoid models

• Published in: Ecotoxicology and environmental safety Vol. 235; p. 113429
• Main Authors: Li, Minghui, Gong, Jing, Gao, Lixiong, Zou, Ting, Kang, Jiahui, Xu, Haiwei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.04.2022; Elsevier
• Subjects: Animals; Brain; Developmental toxicity; Human organoids; Humans; Kidney; Organoids - physiology; Stem cells; Teratogenicity; Developmental toxicity; Human organoids; Teratogenicity; Stem cells
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2022.113429

Tremendous progress has been made in the field of toxicology leading to the advance of developmental toxicity assessment. Conventional animal models and in vitro two-dimensional models cannot accurately describe toxic effects and predict actual in vivo responses due to obvious inter-species differences between humans and animals, as well as the lack of a physiologically relevant tissue microenvironment. Human embryonic stem cell (hESC)- and induced pluripotent stem cell (iPSC)-derived three-dimensional organoids are ideal complex and multicellular organotypic models, which are indispensable in recapitulating morphogenesis, cellular interactions, and molecular processes of early human organ development. Recently, human organoids have been used for drug discovery, chemical toxicity and safety in vitro assessment. This review discusses the recent advances in the use of human organoid models, (i.e., brain, retinal, cardiac, liver, kidney, lung, and intestinal organoid models) for developmental toxicity and teratogenicity assessment of distinct tissues/organs following exposure to pharmaceutical compounds, heavy metals, persistent organic pollutants, nanomaterials, and ambient air pollutants. Combining next-generation organoid models with innovative engineering technologies generates novel and powerful tools for developmental toxicity and teratogenicity assessment, and the rapid progress in this field is expected to continue. •Advances in stem cell techniques for toxicity assessment.•Human organoids can decipher the embryonic development and morphogenesis.•Organoid technologies for developmental toxicology assessment.•Advanced next-generation human organoids toward next-level toxicity testing.