Organoids for toxicology and genetic toxicology: applications with drugs and prospects for environmental carcinogenesis

Advances in three-dimensional (3D) cell culture technology have led to the development of more biologically and physiologically relevant models to study organ development, disease, toxicology and drug screening. Organoids have been derived from many mammalian tissues, both normal and tumour, from adult stem cells and from pluripotent stem cells. Tissue organoids can retain many of the cell types and much of the structure and function of the organ of origin. Organoids derived from pluripotent stem cells display increased complexity compared with organoids derived from adult stem cells. It has been shown that organoids express many functional xenobiotic-metabolising enzymes including cytochrome P450s (CYPs). This has benefitted the drug development field in facilitating pre-clinical testing of more personalised treatments and in developing large toxicity and efficacy screens for a range of compounds. In the field of environmental and genetic toxicology, treatment of organoids with various compounds has generated responses that are close to those obtained in primary tissues and in vivo models, demonstrating the biological relevance of these in vitro multicellular 3D systems. Toxicological investigations of compounds in different tissue organoids have produced promising results indicating that organoids will refine future studies on the effects of environmental exposures and carcinogenic risk to humans. With further development and standardised procedures, advancing our understanding on the metabolic capabilities of organoids will help to validate their use to investigate the modes of action of environmental carcinogens.

Automated summary

Advances in three-dimensional cell culture technology have allowed the development of organoids, which have proven useful for studying organ development, disease, toxicology, and drug screening. Organoids derived from pluripotent stem cells have greater complexity compared to those derived from adult stem cells. These organoids have been beneficial for pre-clinical testing of personalized treatments and in developing large toxicity and efficacy screens. They have also shown promise in environmental and genetic toxicology studies, providing responses similar to those observed in primary tissues and in vivo models.