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

• Published in: Cell stem cell Vol. 30; no. 2; pp. 137 - 152.e7
• Main Authors: Jgamadze, Dennis, Lim, James T., Zhang, Zhijian, Harary, Paul M., Germi, James, Mensah-Brown, Kobina, Adam, Christopher D., Mirzakhalili, Ehsan, Singh, Shikha, Gu, Jiahe Ben, Blue, Rachel, Dedhia, Mehek, Fu, Marissa, Jacob, Fadi, Qian, Xuyu, Gagnon, Kimberly, Sergison, Matthew, Fruchet, Oceane, Rahaman, Imon, Wang, Huadong, Xu, Fuqiang, Xiao, Rui, Contreras, Diego, Wolf, John A., Song, Hongjun, Ming, Guo-li, Chen, Han-Chiao Isaac
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.02.2023
• Subjects: Adult; Animals; brain organoid; brain repair; functional integration; Humans; Induced Pluripotent Stem Cells - physiology; Mammals; Neurons - physiology; Organoids - metabolism; Pluripotent Stem Cells - physiology; Prosencephalon; Rats; Retina; stem cells; visual cortex; stem cells; functional integration; brain organoid; brain repair; visual cortex
• ISSN: 1934-5909; 1875-9777; 1875-9777
• 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. [Display omitted] •Human brain organoids integrate with the injured visual cortex of adult rats•Organoid grafts are synaptically connected to the host retina and visual system•Organoid neurons respond to host visual stimulation and adopt feature selectivity Chen and colleagues demonstrate that human brain organoids can integrate structurally and functionally with the injured adult mammalian brain. Organoid grafts connect synaptically with the rat brain and adopt the function of the visual cortex. These findings support brain organoid transplantation as a therapeutic strategy for restoring cortical function.