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  • Engineering of human brain ...
    Cakir, Bilal; Xiang, Yangfei; Tanaka, Yoshiaki; Kural, Mehmet H; Parent, Maxime; Kang, Young-Jin; Chapeton, Kayley; Patterson, Benjamin; Yuan, Yifan; He, Chang-Shun; Raredon, Micha Sam B; Dengelegi, Jake; Kim, Kun-Yong; Sun, Pingnan; Zhong, Mei; Lee, Sangho; Patra, Prabir; Hyder, Fahmeed; Niklason, Laura E; Lee, Sang-Hun; Yoon, Young-Sup; Park, In-Hyun

    Nature methods, 11/2019, Letnik: 16, Številka: 11
    Journal Article

    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.