Brain organoids: construction, disease modeling and drug discovery

Human brain organoids are three-dimensional, self-organizing structures derived from human embryonic stem cells or pluripotent stem cells, containing a variety of neuronal and glial cell types. Brain organoids have rapidly progressed from early cerebral organoids to a sophisticated toolkit that now includes region-specific models, vascularized constructs, microglia-containing systems, and assembloids, therefore become a unique and useful platform for investigating human brain development.Concurrently, their utility has transcended passive structural recapitulation to encompass disease modeling, functional circuit integration, and drug discovery. Despite these remarkable progress, the field still faces some critical challenges, including pronounced inter-batch variability, limited neuronal maturation, a lack of functional vasculature, and the absence of standardized culture protocols. In this review, we synthesize recent advances in the application of brain organoids to neurodevelopmental and neurological disorders, and to drug discovery, while also outlining future directions and unresolved questions.