Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for ‘replacement’ strategies in several spinal cord disorders.

脊髓神经干细胞（NSC）具有重建受损脊髓神经回路的巨大潜力，但尚未在体外产生。我们现在报告从人类多能干细胞（hPSCs）衍生的脊髓NSC。我们的观察结果表明，这些脊髓神经干细胞分化为脊髓神经元的不同群体，它们沿着背腹轴占据多个位置，并且可以维持较长时间。移植到受伤的脊髓中，富含兴奋性神经元，将大量的轴突延伸到很长的距离，支配了它们的靶结构，并实现了健壮的皮质脊髓再生。移植物突触整合到多个宿主脊髓内和脊髓上系统中，包括皮质脊髓投射，并改善了损伤后的功能结局。