4.6 Article

Production of human spinal-cord organoids recapitulating neural-tube morphogenesis

Journal

NATURE BIOMEDICAL ENGINEERING
Volume 6, Issue 4, Pages 435-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41551-022-00868-4

Keywords

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Funding

  1. Brain Research Program through the National Research Foundation (NRF) - Korean Ministry of Science, ICT and Future Planning [NRF-2015M3C7A1028790, NRF-2017M3C7A1047654, NRF-2017M3A9B3061308, NRF-2021M3E5D9021368]

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A three-dimensional culture system and protocol for the production of human spinal-cord-like organoids have been developed, which recapitulate the morphogenesis of the early spinal cord and can be used for disease modeling and drug screening.
Human spinal-cord-like tissues induced from human pluripotent stem cells are typically insufficiently mature and do not mimic the morphological features of neurulation. Here, we report a three-dimensional culture system and protocol for the production of human spinal-cord-like organoids (hSCOs) recapitulating the neurulation-like tube-forming morphogenesis of the early spinal cord. The hSCOs exhibited neurulation-like tube-forming morphogenesis, cellular differentiation into the major types of spinal-cord neurons as well as glial cells, and mature synaptic functional activities, among other features of the development of the spinal cord. We used the hSCOs to screen for antiepileptic drugs that can cause neural-tube defects. hSCOs may also facilitate the study of the development of the human spinal cord and the modelling of diseases associated with neural-tube defects. A protocol for the production of human spinal-cord-like organoids that recapitulate the tube-forming morphogenesis of the early human spinal cord facilitates screening for antiepileptic drugs that can cause neural-tube defects.

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