Oligodendrogenic neural progenitors for treatment of chronic compressive cervical spinal cord injury

Chronic compressive cervical spinal cord injury (cCSCI), a debilitating condition, lacks effective treatment options. Addressing this gap, our study introduces a novel rat model of cCSCI developed through spinal cord compression via synthetic polyether sheet implantation, closely mimicking human pathology. We evaluated the model's fidelity utilizing a comprehensive series of behavioral, electrophysiological, and histological assessments. Our research also explored the therapeutic potential of oligodendrogenic neural progenitor cells (oNPCs) derived from induced pluripotent stem cells. Transplanted oNPCs successfully integrated into the host spinal cord, differentiated into neurons, astrocytes, and oligodendrocytes, and demonstrated a remarkable capacity for enhancing neuroplasticity. Electrophysiological analyses revealed significant improvements in motor evoked potentials and a rectification of the excitability imbalance posttransplantation, indicating substantial recovery of motor circuits. Histological findings complemented these results, showing enhanced remyelination and a reduction in excitatory transmitter expression in the residual gray matter. Functionally, the transplantation of oNPCs led to marked improvements in grip strength, locomotor abilities, and sensory functions, surpassing those seen with standard treatments. This study not only provides a novel and reliable rat model of cCSCI for further research but also highlights the potential of oNPCs as a transformative approach for spinal cord injury therapy, suggesting their significant role in neural regeneration and repair.