Pluripotent stem cells-based neural organoids for modelling human brain development and diseases

Brain organoids have emerged as transformative in vitro models for studying human neurodevelopment, neural disorders, and evolutionary brain complexity. This review systematically compares neural development in mice and humans, reflecting the limitations of traditional rodent models and highlights the importance of organoid technology. It synthesizes evolutionary, cellular, and molecular perspectives through comprehensive analysis of literature, detailing the evolution of brain organoid technologies, from early "unguided" whole-brain models to region-specific, vascularized, and assembloid systems that recapitulate inter-regional connectivity. The integration of multi-omics approaches including transcriptomics, epigenomics, and proteomics with organoids has enabled rigorous validation of their fidelity to in vivo development and uncovered novel disease mechanisms. We further explore applications of organoids in modeling cellular dynamics, elucidating gene functions, and replicating neurodevelopmental disorders such as autism, microcephaly, and Rett syndrome. Finally, we discuss their utility in high-throughput drug screening and personalized medicine, while addressing ongoing challenges including vascularization, functional maturation, and ethical considerations. Critically, these advances in organoid technology bridge translational gaps by enabling patient-specific disease modeling, accelerating therapeutic discovery, and providing human-relevant platforms to overcome precision neuroscience. By leveraging mouse and human brain organoids to transcend species limitations in neural research, this review offers unprecedented insights into brain development and pathology.