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.

由人类多能干细胞诱导的人类脊髓样组织通常不够成熟，并且不能模仿神经形成的形态特征。在这里，我们报告了一种用于生产人类脊髓样器官 (hSCO) 的三维培养系统和协议，该系统概括了早期脊髓的神经样管形成形态发生。hSCO 表现出神经样管形成形态发生、细胞分化为主要类型的脊髓神经元和神经胶质细胞、成熟的突触功能活动，以及脊髓发育的其他特征。我们使用 hSCO 筛选可能导致神经管缺陷的抗癫痫药物。