From Cells to Organoids: Approaches, Regulatory Mechanisms, Applications, and Challenges of Organoids.

Organoids refer to three-dimensional (3D) multicellular tissues derived from stem cells or single cells through their self-assembly capacity, and significantly, they mimic structural and functional characteristics of the organ from which they are derived. Organoids can maintain the gene expression profiles and mutational features of parental cells during long-term culture. This makes organoids more relevant to the human bodies than gene knockout or overexpression animal models. Consequently, organoids have been widely used in various kinds of fields, including studies on organ developmental mechanisms, regenerative medicine, organ repair, the construction of disease models, high-throughput drug screening, and personalized medicine. Notably, significant progress has recently been made in organoid construction methodologies and regulatory mechanisms. These include the selections of starting cell sources, optimizing matrix materials, and the related cell signaling pathways. The rapid development of organoid technologies has provided new opportunities for their applications in organ transplantation, drug and toxicity screening, and molecular mechanisms for cell and tissue development. In this review, we discuss organoid construction methods involving the starting cell selection and spatiotemporal mediation, regulatory mechanisms with signaling molecules and pathways, and their applications in unveiling organogenesis mechanisms and disease etiology, drug screening, toxicity testing, personalized medicine, regenerative medicine, and alternatives to animal experiments. We also address the perspectives and challenges in this field with an aim to promote the development of organoids in basic research and translational medicine.