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The promises and challenges of human brain organoids as models of neuropsychiatric disease

Nature Medicine volume 22, pages 1220–1228 (2016)Cite this article

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Abstract

Neuropsychiatric disorders such as autism spectrum disorder (ASD), schizophrenia (SCZ) and bipolar disorder (BPD) are of great societal and medical importance, but the complexity of these diseases and the challenges of modeling the development and function of the human brain have made these disorders difficult to study experimentally. The recent development of 3D brain organoids derived from human pluripotent stem cells offers a promising approach for investigating the phenotypic underpinnings of these highly polygenic disorders and for understanding the contribution of individual risk variants and complex genetic background to human pathology. Here we discuss the advantages, limitations and future applications of human brain organoids as in vitro models of neuropsychiatric disease.

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Figure 1: hPSC-based modeling of neuropsychiatric disorders.
Figure 2: Strategies for the generation, characterization and systems-level analysis of 3D cellular models of the human brain.

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Acknowledgements

We thank S. Hyman, L. Rubin, E. Robinson and K. Lilliehook for their critical discussion and suggestions for this manuscript. We are grateful to N. Maria and J. Nguyen for editing of the manuscript, and D. Sun for creating the illustrations for this article. P.A. is a NYSC Robertson Investigator. Work in the Arlotta lab is supported by grants to P.A. the US National Institutes of Health (NS078164 and MH101268), the Stanley Center for Psychiatric Disease of the Broad Institute of MIT and Harvard, and the Harvard Brain Initiative. We apologize to colleagues whose work we could not cite because of space limitations.

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  1. Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA

    Giorgia Quadrato, Juliana Brown & Paola Arlotta

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  1. Giorgia Quadrato
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Correspondence to Paola Arlotta.

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Quadrato, G., Brown, J. & Arlotta, P. The promises and challenges of human brain organoids as models of neuropsychiatric disease. Nat Med 22, 1220–1228 (2016). https://doi.org/10.1038/nm.4214

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