An iPSC-derived neural progenitor cell therapy for subacute spinal cord injury: a phase 1 trial with long-term follow-up

Spinal cord injury (SCI) causes irreversible motor and sensory deficits, and no therapy currently restores the damaged neural circuitry. Previous work has shown that transplantation of induced pluripotent stem cell (iPSC)-derived neural stem/progenitor cells (NS/PCs) restored motor function in preclinical models of subacute SCI; however, the safety of this approach in humans remains unknown. Here we report results from a first-in-human, open-label study of iPSC-NS/PC transplantation in four patients with subacute cervical complete SCI. The primary safety end point was achieved, with no tumor formation or graft-related adverse events observed during 2–4 years of follow-up and stable graft sites on imaging. Exploratory efficacy was assessed as a secondary end point. Median improvement in the International Standards for Neurological Classification of Spinal Cord Injury motor score from baseline (2 weeks after injury) to week 52 was 13 points (range 10–40), with two patients improving in American Spinal Injury Association Impairment Scale (grade A → C and A → D). These gains were numerically greater than spontaneous recovery observed in a registry-based cohort. This study provides clinical evidence that transplantation of human iPSC-NS/PCs into the injured spinal cord is feasible and safe under short-term immunosuppression, with findings supporting further clinical evaluation. The trial is registered at UMIN000035074 , UMIN000050104 and jRCTa031190228 . A phase 1 trial evaluating the safety of iPSC-derived neural stem cell transplantation in subacute complete spinal cord injury, with 2–4 years of follow-up including MRI, neurological and functional assessments met its primary outcome.