Human induced pluripotent stem cell-derived neural stem/progenitor cell therapy for spinal cord injury: preclinical advances and translational perspectives.

Spinal cord injury (SCI) causes irreversible neurological damage and remains a major clinical challenge due to the lack of effective regenerative therapies. Human-induced pluripotent stem cells (hiPSCs) and their derivatives, hiPSC-derived neural stem/progenitor cells (hiPSC-NS/PCs), have demonstrated potential to promote neural repair and functional recovery. The world's first clinical trial using hiPSC-NS/PCs in the subacute phase of SCI has already been initiated. In contrast, chronic SCI-despite accounting for the majority of clinical cases-remains difficult to treat due to pathological barriers such as widespread demyelination, cavitation, scar formation, and persistent inflammation. Recent efforts to overcome these obstacles include combinatorial strategies incorporating rehabilitation, biomaterial scaffolds, pharmacological adjuvants, and robotic-assisted therapy as well as gliogenic or regionally patterned hiPSC-NS/PCs. Preclinical models have demonstrated that such multifaceted approaches can enhance graft survival, axonal regeneration, and functional recovery. In this review, we provide an overview of the biological characteristics, mechanisms of action, and recent advances in preclinical and clinical research on hiPSC-NS/PCs transplantation for SCI. We also discuss future perspectives and challenges toward clinical application. Collectively, these efforts underscore the diverse, innovative, and translational potential of hiPSC-based regenerative medicine for SCI.