2. Academic Validation
  3. Human spinal GABA neurons alleviate spasticity and improve locomotion in rats with spinal cord injury

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

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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