Abstract: Investigating the mechanisms underlying central nervous system disorders is a major scientific issue in the 21st century. However, the inaccessibility and complexity of the human brain have always represented a challenge in understanding the pathophysiology of the central nervous system. Brain organoids are self-assembled three-dimensional aggregates derived from pluripotent stem cells with cell types and structures similar to the embryonic human brain, giving them potential for investigating the atypical cellular, molecular, and genetic characteristics characteristic of central nervous system disorders. Brain organoids also provide a platform for drug screening and serve as a potential source for transplantation therapy for brain injuries. However, the broad application of brain organoids is hampered by several limitations, such as the lack of high-fidelity cell types, insufficient maturation, and considerable heterogeneity, undermining their reliability in specific applications. This review summarizes brain organoid evolution, discusses recent technological and methodological innovations, and reviews their applications in drug screening, transplantation therapy, and disease modeling, as well as clinical research progress. Additionally, we emphasize the limitations of current brain organoid research and explore the potential for advancing the technology to enhance its applicability.

Key words: acute brain injury, bioengineering, brain organoids, brain tissue transplantation, cerebral organoids, drug screening, induced pluripotent stem cell, neurodegenerative diseases, neurodevelopmental disorders