Generating CNS organoids from human induced pluripotent stem cells for modeling neurological disorders

Understanding human brain development and disease is largely hampered by the relative inaccessibility of human brain tissues. Recent advances in human induced pluripotent stem cells (hiPSCs) have led to the generation of unlimited human neural cells and thereby facilitate the investigation of human brain development and pathology. Compared with traditional 2-dimensional (2D) culture methods, culturing the hiPSC-derived neural cells in a three-dimensional (3D) free-floating manner generates human central nervous system (CNS) organoids. These 3D CNS organoids possess the unique advantage of recapitulating multi-regional or region-specific cytoarchitecture seen in the early human fetal brain development. The CNS organoids are becoming a strong complement to the animal model in studying brain development and pathology, and developing new therapies to treat neurodevelopmental diseases. Further improvements to the long-term maintenance and neural maturation of the organoids may allow them to model neurodegenerative diseases. In this review, we will summarize the current development of hiPSCs to generate CNS organoids for modeling neurological disorders and future perspective.