研究动态
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人类前脑器官样体与受伤的成年大鼠视觉系统的结构和功能整合。

Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

发表日期:2023 Feb 02
作者: Dennis Jgamadze, James T Lim, Zhijian Zhang, Paul M Harary, James Germi, Kobina Mensah-Brown, Christopher D Adam, Ehsan Mirzakhalili, Shikha Singh, Jiahe Ben Gu, Rachel Blue, Mehek Dedhia, Marissa Fu, Fadi Jacob, Xuyu Qian, Kimberly Gagnon, Matthew Sergison, Oceane Fruchet, Imon Rahaman, Huadong Wang, Fuqiang Xu, Rui Xiao, Diego Contreras, John A Wolf, Hongjun Song, Guo-Li Ming, Han-Chiao Isaac Chen
来源: Cell Stem Cell

摘要:

由人类多能干细胞创建的脑器官类似体是大脑修复的一种前景性方法,因其可以获取许多大脑的结构特征并具有患者匹配修复的可能。然而,在受伤的成年哺乳动物大脑中,这些实体是否能够与宿主大脑网络整合并不确定。在此,我们提供结构和功能上的证据表明,人脑器官类似体成功地与成年大鼠视觉系统整合,移植到视觉皮层的大损伤空腔中。基于病毒的跨突触追踪揭示了器官类似体神经元与宿主视网膜之间的多突触通道和移植区与视觉系统其他区域之间的相互连接性。宿主动物的视觉刺激引起了器官类似体神经元的响应,包括方向选择性。这些结果表明,人脑器官类似体在插入到大的损伤空腔后有能力采用复杂的功能,这为恢复皮质损伤后的功能提供了一种翻译策略。发表在Elsevier Inc.上。
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 visual 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. Visual 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.Published by Elsevier Inc.