Genta Narazaki, Yuki Miura, Sergey D. Pavlov, Mayuri Vijay Thete, Julien G. Roth, Merve Avar, Sungchul Shin, Ji-il Kim, Zuzana Hudacova, Sarah C. Heilshorn, Sergiu P. Pașca
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Scalable production of human cortical organoids using a biocompatible polymer
The generation of neural organoids from human pluripotent stem cells holds great promise in modelling disease and screening drugs, but current approaches are difficult to scale due to undesired organoid fusion. Here we develop a scalable cerebral cortical organoid platform by screening biocompatible polymers that prevent the fusion of organoids cultured in suspension. We identify a cost-effective polysaccharide that increases the viscosity of the culture medium, significantly enhancing the yield of cortical organoids while preserving key features such as regional patterning, neuronal morphology and functional activity. We further demonstrate that this platform enables straightforward screening of 298 FDA-approved drugs and teratogens for growth defects using over 2,400 cortical organoids, uncovering agents that disrupt organoid growth and development. We anticipate this approach to provide a robust and scalable system for modelling human cortical development, and facilitate efficient compound screening for neuropsychiatric disorders-associated phenotypes.
期刊介绍:
Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.