Generation of spinal cord organoids from human induced pluripotent stem cells caudalised to a lumbar fate.

Organoids offer a powerful platform to model human development and disease in vitro, while preserving key features of in vivo tissue architecture and complexity. In this study, we developed a protocol to generate human induced pluripotent stem cell (iPSC)-derived spinal cord organoids patterned to the lumbar region. Through immunofluorescent labelling and single-cell RNA sequencing analyses of these lumbar spinal cord organoids, we identified an enriched neuronal population complemented by a diverse array of glial subtypes that successfully recapitulate the ventral spinal cord, demonstrating greater anatomical relevance than conventional 2D motor neuron cultures. Notably, these organoids displayed functional neuronal properties, including spontaneous activity, indicative of integrated neural networks. This spinal cord organoid platform provides a physiologically relevant model for investigating human spinal cord development and presents a promising tool for studying neurodegenerative diseases and spinal cord injury in a controlled, human-specific context.