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.
Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide an excellent platform to study human brain development and diseases in complex 3D tissue. However, current ...hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. Here, we engineered hESCs to ectopically express human ETS variant 2 (
hETV2
) to create
in vitro
vasculature in hCOs, namely vhCOs (vascularized hCOs).
hETV2
-expressing cells in hCOs contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vascularization resulted in enhanced functional maturation of organoids. We found that vhCOs acquired several blood-brain barrier (BBB) characteristics, including an increase in the expression of tight junctions, nutrient transporters, and trans-endothelial electrical resistance. Finally,
hETV2
-induced endothelium supported the formation of perfused blood vessels
in vivo
. These vhCOs form vasculature that resemble the early prenatal brain, and present a robust model to study brain disease
in vitro
.
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