Engineered human mini-brains, made possible by knowledge from the convergence of precision microengineering and cell biology, permit systematic studies of complex neurological processes and of pathogenesis beyond what can be done with animal models. By culturing human brain cells with physiological microenvironmental cues, human mini-brain models reconstitute the arrangement of structural tissues and some of the complex biological functions of the human brain. In this Review, we highlight the most significant developments that have led to microphysiological human mini-brain models. We introduce the history of mini-brain development, review methods for creating mini-brain models in static conditions, and discuss relevant state-of-the-art dynamic cell-culture systems. We also review human mini-brain models that reconstruct aspects of major neurological disorders under static or dynamic conditions. Engineered human mini-brains will contribute to advancing the study of the physiology and aetiology of neurological disorders, and to the development of personalized medicines for them.
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The authors thank W.-B. Tay (Ministry of Education, Singapore) and S. Neo (National University of Singapore) for proofreading the manuscript. This work was supported by the National Research Foundation (nos. NRF-2020R1A2C2010285 and NRF-2018M3C7A1056896 to H.C.)
The authors declare no competing interests.
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Tan, HY., Cho, H. & Lee, L.P. Human mini-brain models. Nat Biomed Eng 5, 11–25 (2021). https://doi.org/10.1038/s41551-020-00643-3