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Human mini-brain models

Abstract

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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Fig. 1: Neuronal damage mediated by dynamical mechanical cues leads to the alteration of neurovascular homeostasis.

Image courtesy of You Jung Kang, University of North Carolina at Charlotte

Fig. 2: Main techniques for the creation of human mini-brain models.
Fig. 3: Examples of mini-brain models using dynamic culture.
Fig. 4: Major neurological disorders recapitulated with mini-brain models under static or dynamic conditions.

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Acknowledgements

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.)

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L.P.L. and H.C. shaped ideas and provided guidance. H.Y.T. and H.C. researched data for the article. H.Y.T. prepared the figures and wrote the manuscript with assistance from H.C. and L.P.L. All authors contributed to discussion of the contents, and reviewed and edited the manuscript.

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Correspondence to Hansang Cho or Luke P. Lee.

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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

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