期刊
NATURE METHODS
卷 16, 期 11, 页码 1169-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41592-019-0586-5
关键词
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资金
- NIH [GM111667-01, R01AA025080-01, R01CA203011-2, R01HL127759, DP3DK108245, 1R21 EB024889, 1R01 HL148819, EB023366-02, MH067528-02]
- CSCRF [14-SCC-YALE-01, 16-RMB-YALE-04]
- Kavli Foundation
- Simons Foundation
- KRIBB/KRCF research initiative program [NAP-09-3]
- College of Medicine, University of Arkansas for Medical Sciences from the IDeA program at NIGMS [P30 GM110702]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute, Republic of Korea [HI15C2782, HI16C2211]
- Fonds de recherche du Quebec - Sante in Canada
- Korea Health Promotion Institute [HI15C2782000019, HI16C2211010019] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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