Abstract
Research on cell therapy for spinal cord injury has yet to achieve sufficient functional recovery. Previous studies in the field grafted oligodendrocyte progenitors, nonspinal neural stem cells or primary spinal neural progenitors. Here we sought to improve functional outcomes by grafting clinically compatible spinal cord neural stem cells derived from human embryonic stem cells (H9-scNSCs). H9-scNSCs significantly improved functional outcomes on a skilled hand task 9.2-fold (P = 2.5 × 10-27) in hemisected subjects compared with lesioned controls, achieving a fine object retrieval success of 53.4 ± 19.2%, and 2.9-fold (P = 6.3 × 10-8) superior to controls in hemicontused subjects. Recovery correlated with rehabilitation effort. Grafts extended up to hundreds of thousands of new axons into host circuits up to 39 mm below the injury, forming synapses with host circuitry. Lesion fill was substantially higher and differentiated cell-fate distributions were much closer to that of the normal spinal cord than in previous studies using primary spinal cord cells, likely enabling the observed superior functional outcomes.