Human spinal GABA neurons alleviate spasticity and improve locomotion in rats with spinal cord injury
Chen-Zi 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, Tie-Cheng Guo, Xiaohua Han, Su‐Chun Zhang, Wei Wang, Hong Chen
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.