Human Spinal Gaba Neurons Alleviate Spasticity And Improve Locomotion In Rats With Spinal Cord Injury

Spinal cord injury (SCI) often results in spasticity. There is currently no effective therapy for spasticity. Here, we describe a method to efficiently differentiate human pluripotent stem cells from spinal GABA neurons. After transplantation into the injured rat spinal cord, the DREADD (designer receptors exclusively activated by designer drug)-expressing spinal progenitors differentiate into GABA neurons, mitigating spasticity-like response of the rat hindlimbs and locomotion deficits in 3 months. Administering clozapine-N-oxide, which activates the grafted GABA neurons, further alleviates spasticity-like response, suggesting an integration of grafted GABA neurons into the local neural circuit. These results highlight the therapeutic potential of the spinal GABA neurons for SCI.