Cakir et al., Nature Method, 2019

Nat Methods. 2019 Nov;16(11):1169-1175. doi: 10.1038/s41592-019-0586-5. Epub 2019 Oct 7.

Engineering of human brain organoids with a functional vascular-like system

Bilal Cakir # 1Yangfei Xiang # 1Yoshiaki Tanaka 1Mehmet H Kural 2Maxime Parent 3Young-Jin Kang 4 5Kayley Chapeton 6Benjamin Patterson 1Yifan Yuan 2Chang-Shun He 7Micha Sam B Raredon 2 7Jake Dengelegi 8Kun-Yong Kim 1Pingnan Sun 1Mei Zhong 9Sangho Lee 10Prabir Patra 1 8Fahmeed Hyder 3 7Laura E Niklason 2 7Sang-Hun Lee 4 5Young-Sup Yoon 10 11In-Hyun Park 12Affiliations expand


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.

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Categories: 2019