Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
Stem Cell Reports. 2020 Aug 11;15(2):467-481. doi: 10.1016/j.stemcr.2020.06.016. Epub 2020 Jul 16.
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.
通过细胞替代来重建缺失的神经回路是治疗大脑皮质损伤后神经功能缺损的一种可能方法。类脑器官可以成为细胞移植的新来源，但由于类器官的细胞组成会随其发育时间的变化而改变，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，我们将分化后 6 周或 10 周的人胚胎干细胞源性脑类器官（6w-或 10w-类器官）移植到小鼠大脑皮质中。6w-类器官沿着皮质脊髓束延伸出更多的轴突，但移植后会导致过度生长，有更高比例的增殖细胞。10w-类器官的轴突延伸数量较少，但在脑损伤后 1 周移植时会增强。最后，10w-类器官在食蟹猴脑中延伸了轴突。这些结果为脑损伤和中风的细胞替代治疗的发展提供了帮助。
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