Generation of vascularized brain organoids to study neurovascular interactions
Xin-Yao Sun,
Xiang-Chun Ju,
Yang Li,
Peng-Ming Zeng,
Jian Wu,
Ying-Ying Zhou,
Li-Bing Shen,
Jian Dong,
Yue-Jun Chen,
Zhen-Ge Luo
Affiliations
Xin-Yao Sun
School of Life Science and Technology, ShanghaiTech University, Shanghai, China; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China
Xiang-Chun Ju
Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
Yang Li
School of Life Science and Technology, ShanghaiTech University, Shanghai, China
Peng-Ming Zeng
School of Life Science and Technology, ShanghaiTech University, Shanghai, China
Jian Wu
School of Life Science and Technology, ShanghaiTech University, Shanghai, China
Ying-Ying Zhou
Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China
Li-Bing Shen
Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
Jian Dong
School of Life Science and Technology, ShanghaiTech University, Shanghai, China
Yue-Jun Chen
Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China
Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids, respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood–brain barrier-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, particularly the vasculature and microglia niche.
