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Progress in understanding human brain biology and related brain disorders has been remarkably slow due to limited access to functional brain tissue. This has hampered the development of effective therapies for several neurological disorders. Emerging technologies based on 3D brain organoids derived from human ...

Progress in understanding human brain biology and related brain disorders has been remarkably slow due to limited access to functional brain tissue. This has hampered the development of effective therapies for several neurological disorders. Emerging technologies based on 3D brain organoids derived from human pluripotent stem cells (hPSCs) enable the modeling of complex aspects of human brain development and function. Over the last decade, a flurry of protocols has been developed aiming to establish 3D stem models that resemble various brain regions and better recapitulate aspects of human brain physiology compared to classical monolayer methods. The latest state-of-art protocols include the assembly of multi-region brain organoids (fused brain organoids or “assembloids”) which allow for the monitoring and assessment of phenomena that have been previously inaccessible, such as the emergence of interregional connectivity.
Despite recent advances, current 3D brain organoid models suffer from several limitations such as reproducibility, in vivo fidelity, neuronal maturation, and spatial organization, topics that are poised to inform future brain organoid efforts.

This Research Topic welcomes original research, review, and commentary articles aimed to explore all recent advances in human in vitro models based on 3D brain organoids. A special focus is the research on brain organoids representing defined brain regions, multi-organoid/lineage systems towards reconstructing inter-regional/lineage cross-talks, efforts to improve the fidelity and reproducibility of derived systems, and bioengineering & synthetic biology techniques to enable spatio-organizational control. Improved protocols will strengthen the ability for robust disease modeling using patient-derived cells which remains one of the core promises of hPSC-based models of human brain organogenesis.

Combined with orthogonal modeling approaches such as in vivo murine models of disease and primary tissue whenever available, brain organoids will bring us one step closer to understanding how the human brain develops, functions, and malfunctions.

Keywords: Brain Organoids, Assembloids, Human Brain Organogenesis, Neurophysiology, Neurodevelopmental Disorders


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