Human spinal cord organoids exhibiting neural tube morphogenesis for a quantifiable drug screening system of neural tube defects

Abstract

The human spinal cord forms well-organized neural circuits for environment sensing and motor behavior. The three-dimensional (3D) induction of the spinal cord-like tissue from human pluripotent stem cells has been reported, but they often do not mimic morphological features of neurulation and their maturity is limited. Here, we report an advanced 3D culture system for the production of human spinal cord-like organoids (hSCOs) suitable for the scale-up and quantitative studies. The hSCOs exhibited many aspects of spinal cord development, including neurulation-like tube-forming morphogenesis, differentiation of the major spinal cord neurons and glial cells, and mature synaptic functional activities. We further demonstrated that hSCOs platform allowed quantitative and systematic high-throughput examination of the potential risk of neural tube defects induced by antiepileptic drugs. Thus, hSCOs can be used for understanding human spinal cord development, disease modeling, and toxicology screening.