Abstract:
: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.
journal_name
Nat Methodsjournal_title
Nature methodsauthors
Cakir B,Xiang Y,Tanaka Y,Kural MH,Parent M,Kang YJ,Chapeton K,Patterson B,Yuan Y,He CS,Raredon MSB,Dengelegi J,Kim KY,Sun P,Zhong M,Lee S,Patra P,Hyder F,Niklason LE,Lee SH,Yoon YS,Park IHdoi
10.1038/s41592-019-0586-5subject
Has Abstractpub_date
2019-11-01 00:00:00pages
1169-1175issue
11eissn
1548-7091issn
1548-7105pii
10.1038/s41592-019-0586-5journal_volume
16pub_type
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