Spinal segment-specific properties of neural stem cells contribute to the outcomes of spinal cord injury repair

Neurons in distinct spinal cord segments serve specific functions, raising questions about whether human spinal cord-derived neural stem cells (hscNSCs) retain segment-specific properties crucial for spinal cord injury (SCI) repair. We established a culture system amplifying hscNSCs from cervical, thoracic, and lumbar segments, revealing segment-specific transcriptional profiles and differentiation potentials. Notably, thoracic hscNSCs exhibited elevated hepatocyte growth factor (HGF) expression inherited from the pre-ganglionic column, enhancing their differentiation into motor neurons. Transplantation of thoracic hscNSCs into thoracic SCI rat models demonstrated superior graft survival, neural regeneration, and functional recovery compared with cervical or lumbar counterparts. Thoracic hscNSCs reduced inflammation, minimized glial scar formation, and significantly improved locomotor function post-SCI. Our findings underscore the importance of segment-specific properties of hscNSCs in optimizing SCI repair outcomes, paving the way for tailored therapeutic strategies in spinal cord regeneration.