Advances of organoids in the study of nervous system diseases: A narrative review

Traditional two-dimensional cellular models and patient-derived xenograft models have limitations in simulating human brain structure and function. In recent years, brain organoid technology has emerged as a novel three-dimensional tissue culture method, offering new avenues for studying neurological diseases. The purpose of this review is to overview the development of brain organoid technology with a focus on its applications in cerebrovascular diseases, brain tumors, and neurodegenerative disorders, as well as to discuss current challenges and future directions. Brain organoid technology enables more realistic reproduction of disease states by simulating the three-dimensional structure of the human brain. In cerebrovascular diseases, vascularized brain organoids offer a novel model for research, despite the existing limitations in vascularization. In brain tumor research, this technology can construct the models that closely resemble the tumor characteristics of patients, thereby uncovering the molecular mechanisms underlying tumorigenesis. In neurodegenerative diseases, brain organoid technology facilitates the exploration of disease pathology and potential therapeutic strategies. Compared with traditional models such as two-dimensional cell cultures, brain organoid technology provides a more physiologically relevant environment for studying complex cell-cell and cell-microenvironment interactions. In the field of cerebrovascular diseases, researchers have developed five methods for vascularizing brain organoids: co-culture with endothelial cells, co-culture with vascular organoids, organoid-on-a-chip technology, three-dimensional bioprinting of organoids, spontaneous vascularization of brain organoids, and the establishment of stroke organoid models. Various brain tumor organoid models, such as glioblastoma, medulloblastoma, and meningioma, have been successfully established. Similarly, organoid models for neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, have also been developed. Brain organoid technology offers a powerful tool for disease modeling in the field of neuroscience, enhancing our understanding of the mechanisms underlying neurological disorders and the development of novel therapeutic approaches.