• Transplanted cerebrospinal fluid-contacting neurons (CSF-cNs) survive long-term in vivo and differentiate into motor neurons in a mouse model of spinal cord injury.
• CSF-cNs form synaptic connections with host neurons, as evidenced by co-expression of SYN, GAD65/67, and vGLUT1 at 8 weeks post-transplantation.
• Transplantation of CSF-cNs significantly improves motor function recovery, with higher BMS scores and more coordinated gait compared to PBS control.
• CSF-cNs reduce cavity formation at the injury site, indicating a neuroprotective and regenerative effect.