Injury and therapy in a human spinal cord organoid.

Damage to the spinal cord can lead to irreversible paralysis and loss of sensory function, but translation of preclinical therapies remains elusive. We recently showed that bioactive supramolecular assemblies of peptide amphiphiles can reverse paralysis in an acute mouse model following severe spinal cord injury (SCI). Here we report the development of two human spinal cord organoid injury models to simulate SCI in vitro, a laceration of the organoid with a scalpel and a compressive contusion commonly used in preclinical models, both resulting in immediate neuronal death and the formation of glial scar-like tissue. Treatment of the injured organoids with the preclinical therapy suppressed the scar-like tissue and promoted significant axonal regeneration, as observed previously in vivo. With the inclusion of microglia into the spinal cord organoids, we demonstrate that the supramolecular nanomaterial reduced pro-inflammatory factors commonly associated with injury. The human spinal cord organoid models developed here could accelerate the discovery of therapies to treat SCI and possibly damage of other central nervous system tissues owing to trauma or disease.