The in vivo regenerative capacity of neuromesodermal progenitor derived spinal cord neurons in a spinal cord injury model

Spinal cord injury (SCI) is a severe neurological condition, typically caused by trauma, leading to neuronal loss in the gray matter, axonal disruption in the white matter, and conduction block across spinal pathways. The primary injuries trigger progressive neurodegeneration along upper motor tracts, particularly the corticospinal tract. Initial treatment involves surgery and then corticosteroids, which may limit secondary damage but do not restore tissue or function. In addition, the current clinical rehabilitation therapies remain inadequate, and cell-based approaches have not yet been clinically standardized and require on supportive biomaterials. The in vivo preclinical study evaluated the regenerative potential of NMP-derived human spinal neurons in a T10 semi-cut SCI model using 45 male Balb/c mice. D0 (undifferentiated) and D30 (differentiated) hPSCs were transplanted into the lesion via matrigel-dome, and compared to a vehicle group. Axonal regeneration (BDA tracing), neuronal survival (cresyl violet, NeuN), glial scarring (GFAP), and functional recovery (Basso mouse scale, horizontal ladder walk, open field tests) were systematically assessed. As a result of in vivo study, the cells reduced glial scar functionally, stopped degeneration by suppressing neuronal survival, moved rostro-caudally beyond the lesion site, extending axons showed by BDA, contributed to tissue repair via self-renewal of the cell source, and achieved motor recovery as much as unparalyzed. The study highlights NMP-derived spinal neurons as a potential therapy for SCI, promoting motor recovery and neural regeneration. Their stable profile of cells offer a strategic link between personalized and large-scale therapies, supporting both autologous and allogeneic cell banking, and may be further enhanced by integration with scaffolds to improve viability and engraftment.