Injury and Treatment of a Human Spinal Cord Organoid II

Damage of the spinal cord, which can lead to irreversible paralysis and loss of sensory function, is among the most devastating injuries suffered by humans. A significant effort has been made over the past few decades to find potential therapies to treat spinal cord injury (SCI), an objective that faces the challenge of central nervous system regeneration. Experimental access to human spinal cord tissue is therefore a critical need for discovery of SCI therapies and thus availability of the organ mimics known as organoids offers great potential. Research on spinal cord organoids has been sparse and only very recently enabled by the discovery of the necessary human progenitor cells derived from pluripotent stem cells. We report here on a human organoid model to simulate SCI in vitro and test the potential of novel therapies. We found that the model, involving injury of the organoid with a sharp scalpel, reveals immediate neuronal death and subsequently generates the characteristic glial scar observed after injury with its biological markers. Exposure of the injured organoid to a recently discovered pre-clinical therapy for SCI avoids formation of the scar and promotes axon regeneration in the area of the lesion. Furthermore, in the absence of injury we directly observed the activation of the developmental program to extend axons by the tested therapy, which contains bioactive nanofibers with intense supramolecular motion. The model developed here could accelerate discovery of therapeutic strategies to treat the broad spectrum of spinal cord injuries. Comparative gene expression profiling analysis of single cell RNA-seq data for human spinal cord organoids at two stages (5 weeks and 14 weeks in culture).