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.
Keywords: DREADD; H-reflex; clozapine-N-oxide; human embryonic stem cell; human pluripotent stem cells; rats; somatosensory GABA neurons; spasticity; spinal cord injury; stem cell transplantation.
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.