Organoids for disease modeling and treatment: state-of-the-art

The emergence of organoids has received widespread attention for faithful recapitulation of physiological and pathological conditions, together with overcoming the major bottleneck of extrapolating laboratory findings from model systems to human organs. Organoid technologies are one of the most revolutionary breakthroughs in the fields of regenerative medicine and biomedical research. These three-dimensional (3D) micro-organ models are derived from stem cells and tissue derivatives, and can highly simulate the structure and function of parental organs, which thus open up unprecedented avenues for understanding organogenesis, disease modeling, drug screening and individualized therapeutics. In this review, we comprehensively elaborate on the core principles and key elements of organoid construction, and the multidisciplinary integration with the advanced technologies. Simultaneously, we systematically summarize their applications in disease modeling and pharmaceutical research, together with the landscape of organoid-based observational and interventional clinical trials in regenerative medicine. Furthermore, we put forward the outstanding prospects and challenges in organoid-based precise diagnosis and treatment applications. In particular, the long-standing key issues in the field such as vascularization and maturity, standardization and reproducibility, biobank and ethical considerations, and the emerging interdisciplinary integrations. Collectively, we outline the state-of-the-art renewal in organoid-guided precision medicine and regenerative medicine, which will benefit the following investigations in development biology and clinical translation.