Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Stem Cell. 2023 Feb 2;30(2):137-152.e7. doi: 10.1016/j.stem.2023.01.004.
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.
从人类多能干细胞中创建的大脑类器官代表了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，并提高了匹配患者进行修复的可能性。然而，在成年哺乳动物大脑损伤的背景下，这些实体是否能够与宿主大脑网络整合，目前还没有得到很好的证实。在这里，我们提供了结构和功能上的证据，表明人类大脑类器官在移植到视皮层的大损伤腔后，可以成功地与成年大鼠的视觉系统整合。基于病毒的跨突触示踪显示，类器官神经元与宿主视网膜之间存在多突触通路，并且移植物与视觉系统的其他区域之间存在相互连接。对宿主动物进行视觉刺激会引起类器官神经元的反应，包括方向选择性。这些结果表明，人类大脑类器官在插入大损伤腔后具有采用复杂功能的能力，这为皮质损伤后恢复功能提供了一种转化策略。
