Human spinal GABA neurons alleviate spasticity and improve locomotion in rats with spinal cord injury

Cell Rep. 2021 Mar 23;34(12):108889. doi: 10.1016/j.celrep.2021.108889.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Cell Differentiation
  • Cell Survival
  • GABAergic Neurons / pathology*
  • Humans
  • Locomotion
  • Lumbar Vertebrae / pathology
  • Lumbar Vertebrae / physiopathology
  • Male
  • Motor Neurons / pathology
  • Motor Neurons / ultrastructure
  • Muscle Spasticity / complications
  • Muscle Spasticity / pathology*
  • Muscle Spasticity / physiopathology*
  • Neural Inhibition
  • Pluripotent Stem Cells / metabolism
  • Pluripotent Stem Cells / transplantation
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / pathology*
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / physiopathology*
  • Spinal Cord Injuries / therapy
  • Synapses / metabolism
  • Synapses / ultrastructure