Structural and functional integration of human forebrain organoids with the injured adult rat visual system
Structural and functional integration of human forebrain organoids with the injured adult rat visual system
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DOI：
10.1016/j.stem.2023.01.004
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发表时间：
2023-02-02
期刊：
影响因子：
23.9
通讯作者：
Chen, Han-Chiao Isaac
中科院分区：
文献类型：
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作者：
Jgamadze, Dennis;Lim, James T.;Chen, Han-Chiao Isaac
由人类多能干细胞创造的脑器官是一种很有前途的脑修复方法。它们获得了大脑的许多结构特征，并提高了患者匹配修复的可能性。这些实体是否能在受损的成年哺乳动物脑的背景下与宿主脑网络整合还没有很好的确定。在这里，我们提供了结构和功能的证据，证明人脑有机化合物成功地与成年大鼠的视觉系统结合后，移植到视神经皮质的大损伤腔中。基于病毒的跨突触追踪揭示了器官神经元和宿主视网膜之间的多突触路径，以及移植物和视觉系统其他区域之间的相互连接。VI-sual刺激宿主动物可引起器质神经元的反应，包括定向选择性。这些结果证明了人脑器官在插入大的损伤腔后具有复杂功能的能力，提示了一种在皮质损伤后恢复功能的翻译策略。
Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the vi-sual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Vi-sual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.