Cell Reports (Mar 2021)
Human spinal GABA neurons alleviate spasticity and improve locomotion in rats with spinal cord injury
- ChenZi Gong,
- Xiaolong Zheng,
- FangLiang Guo,
- YaNan Wang,
- Song Zhang,
- Jing Chen,
- XueJiao Sun,
- Sayed Zulfiqar Ali Shah,
- YiFeng Zheng,
- Xiao Li,
- Yatao Yin,
- Qian Li,
- XiaoLin Huang,
- Tiecheng Guo,
- Xiaohua Han,
- Su-Chun Zhang,
- Wei Wang,
- Hong Chen
Affiliations
- ChenZi Gong
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Xiaolong Zheng
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- FangLiang Guo
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- YaNan Wang
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Song Zhang
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Jing Chen
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- XueJiao Sun
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Sayed Zulfiqar Ali Shah
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- YiFeng Zheng
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Xiao Li
- School of Mechanical Engineering, Hubei University of Technology, Wuhan 430068, China
- Yatao Yin
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Qian Li
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- XiaoLin Huang
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Tiecheng Guo
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Xiaohua Han
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Su-Chun Zhang
- 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
- Wei Wang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Corresponding author
- Hong Chen
- Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Corresponding author
- Journal volume & issue
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Vol. 34,
no. 12
p. 108889
Abstract
Summary: 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.
