The reconstruction of lost neural circuits by cell replacement is a possible treatment for neurological deficits after cerebral cortex injury. Cerebral organoids can be a novel source for cell transplantation, but because the cellular composition of the organoids changes along the time course of the development, it remains unclear which developmental stage of the organoids is most suitable for reconstructing the corticospinal tract. Here, we transplanted human embryonic stem cell-derived cerebral organoids at 6 or 10 weeks after differentiation (6w- or 10w-organoids) into mouse cerebral cortices. 6w-organoids extended more axons along the corticospinal tract but caused graft overgrowth with a higher percentage of proliferative cells. Axonal extensions from 10w-organoids were smaller in number but were enhanced when the organoids were grafted 1 week after brain injury. Finally, 10w-organoids extended axons in cynomolgus monkey brains. These results contribute to the development of a cell-replacement therapy for brain injury and stroke.

通过细胞置换重建失去的神经回路是对大脑皮层损伤后神经功能缺损的一种可能的治疗方法。脑类器官可能是一种新的细胞移植来源，但是由于类器官的细胞组成会随着发育过程的变化而变化，因此尚不清楚类器官的哪个发育阶段最适合重建皮质脊髓束。在这里，我们在分化后的6或10周（6w或10w的类生物体）将人类胚胎干细胞衍生的脑类器官移植到小鼠的大脑皮层中。6w-类生物素沿皮质脊髓束延伸更多的轴突，但导致移植物过度生长，并带有较高百分比的增殖细胞。10w-类器官的轴突延伸数量较少，但在脑损伤后1周移植类器官时，轴突延伸得到增强。最后，10w类生物体在食蟹猴大脑中扩展了轴突。这些结果有助于开发用于脑损伤和中风的细胞替代疗法。