Brain organoids and brain disease organoids modeling in the age of artificial intelligence

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Abstract The human brain governs bodily functions with exceptional complexity, yet neuroscience research is hindered by limited access to authentic human tissues, restricted availability of region-specific specimens, and a lack of physiologically relevant experimental models. Brain organoids and disease-specific brain organoids have emerged as transformative research platforms to address these bottlenecks. This review systematically summarizes advances in normal brain organoids, including cortical, cerebellar, meningeal, cerebrovascular, and blood–brain barrier models, as well as disease organoids recapitulating glioma, neurodegeneration, psychiatric disorders, neurodevelopmental defects, epilepsy, stroke and other neurological conditions. We highlight seven key translational advances of brain organoids in targeted therapy development, drug discovery and repurposing, brain–organ crosstalk, tumor brain metastasis, and longevity research. We further discuss the frontier interplay between carbon-based brain organoids and silicon-based artificial intelligence. Integrating stem cell biology, tissue engineering and clinical neuroscience, brain organoids greatly advance mechanistic research of neurological diseases and provide promising platforms for personalized medicine and regenerative therapeutics.

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