4.8 Article

Generation of vascularized brain organoids to study neurovascular interactions

Journal

ELIFE
Volume 11, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.76707

Keywords

brain organoid; brain vasculature; neural progenitors; blood-brain-barrier; microglia; None

Categories

Funding

  1. National Key Research and Development Program of China [2021ZD0202500, 2017YFA0700500]
  2. National Natural Science Foundation of China [32130035, 92168107, 31871034]
  3. Chinese Academy of Sciences Key Project [QYZDJ-SSW-SMC025]
  4. Shanghai Municipal People's Government [2018SHZDZX05, 201409001700]

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This study successfully fused blood vessels and brain organoids to obtain vascularized brain organoids. The fused organoids not only had vascular network-like structures and increased number of neural progenitors, but also contained functional blood-brain barrier-like structures and microglial cells with immune functions.
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.

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