Development of human brain organoids with functional vascular-like system

By Bilal Cakir, Yangfei Xiang, Yoshiaki Tanaka, M. Kural, Maxime J Parent, Young‐Jin Kang, Kayley Chapeton, Benjamin Patterson, Yifan Yuan, Changshun He and 11 more. Nature Methods, 2019

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Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide a platform to study human brain development and diseases in complex three-dimensional tissue. However, current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. We engineered hESCs to ectopically express human ETS variant 2 (ETV2). ETV2-expressing cells in hCOs contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vasculature-like structures resulted in enhanced functional maturation of organoids. We found that vascularized hCOs (vhCOs) acquired several blood-brain barrier characteristics, including an increase in the expression of tight junctions, nutrient transporters and trans-endothelial electrical resistance. Finally, ETV2-induced endothelium supported the formation of perfused blood vessels in vivo. These vhCOs form vasculature-like structures that resemble the vasculature in early prenatal brain, and they present a robust model to study brain disease in vitro. Expression of ETV2 in human cortical organoids induces the formation of vascular-like networks, which reduces cell death within organoids and increases their functional maturation.

Subfields: Biomedical Engineering, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7469a3affd976bb12cf17c33e9f69d42b15fba6c