Organoids pharmacology and toxicology

Abstract

Model evolution is crucial for understanding the effects and safety of drugs in pharmacological and toxicological research. Traditional cell lines and animal models have contributed significantly to drug development. Nonetheless, cell lines lack the complex architecture and cell–cell interactions of real organs, and animal models may not accurately predict human responses because of species differences. Organoids are in vitro models that closely mimic the architecture and function of native organs, enabling them to more accurately reflect the physiological and pathological states of the human body and fill the gap between traditional models and in vivo human studies. They show great potential for organ development, disease progression, and preclinical drug screening. This review comprehensively analyzes the impact of organoid technology on pharmacological and toxicological models; explores their applications in drug screening, toxicity assessment, and mechanistic research; and discusses the current limitations and future prospects of organoid pharmacology and toxicology, providing a theoretical basis for promoting the development of more effective and safer drugs. Patient-derived organoids (PDOs), as three-dimensional in vitro models, establish a clinically relevant biomimetic platform for drug toxicology and efficacy assessment by faithfully preserving the histopathological features and genetic landscape of native tissues. Their inherent 3D architecture and cellular heterogeneity can accurately simulate the individualized treatment response, significantly improve the preclinical prediction ability, and reduce the dependence on animal experiments. This technology facilitates the optimization of drug screening, the analysis of toxicity mechanism and the development of precision medicine, and provides an efficient and reliable platform for translational medicine research.

Topics & Concepts