Advanced human developmental toxicity and teratogenicity assessment using human organoid models

Area of Science:

• Toxicology
• Developmental Biology
• Stem Cell Research

Background:

• Conventional animal and 2D in vitro models inadequately predict human developmental toxicity due to inter-species differences and lack of physiological relevance.
• Human embryonic stem cell (hESC)- and induced pluripotent stem cell (iPSC)-derived organoids provide complex, multicellular, organotypic models that recapitulate human organogenesis.

Purpose of the Study:

• To review recent advances in utilizing human organoid models for developmental toxicity and teratogenicity assessment.
• To highlight the application of organoids in evaluating the impact of various toxicants on diverse human organ systems.

Main Methods:

• Review of current literature on human organoid models (brain, retinal, cardiac, liver, kidney, lung, intestinal).
• Discussion of organoid applications in assessing toxicity from pharmaceuticals, heavy metals, pollutants, nanomaterials, and air pollutants.
• Integration of organoid models with innovative engineering technologies.

Main Results:

• Human organoids accurately model human organ development, cellular interactions, and molecular processes.
• Organoids are effective in vitro tools for assessing developmental toxicity and teratogenicity across multiple organ systems.
• Emerging organoid technologies combined with engineering offer powerful new assessment tools.

Conclusions:

• Human organoid models represent a significant advancement over traditional methods for developmental toxicity assessment.
• The use of organoids is crucial for understanding and predicting the effects of environmental and pharmaceutical exposures on human development.
• Continued progress in organoid technology promises to further revolutionize safety and toxicity testing.