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.
ChenZi Gong  1 ,  Xiaolong Zheng  2 ,  FangLiang Guo  2 ,  YaNan Wang  1 ,  Song Zhang  1 ,  Jing Chen  1 ,  XueJiao Sun  1 ,  Sayed Zulfiqar Ali Shah  1 ,  YiFeng Zheng  1 ,  Xiao Li  3 ,  Yatao Yin  1 ,  Qian Li  1 ,  XiaoLin Huang  1 ,  Tiecheng Guo  1 ,  Xiaohua Han  1 ,  Su-Chun Zhang  4 ,  Wei Wang  5 ,  Hong Chen  6
Affiliations
  • 1. Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 3. School of Mechanical Engineering, Hubei University of Technology, Wuhan 430068, China.
  • 4. Waisman Center, Department of Neuroscience and Department of Neurology, University of Wisconsin, Madison, WI, USA; Program in Neuroscience & Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore.
  • 5. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: [email protected].
  • 6. Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: [email protected].
PMID: 33761348 DOI: 10.1016/j.celrep.2021.108889
Abstract

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.
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