Engineering of Human Brain Organoids with a Functional Vascular-like System

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2019 Oct 9

PMID 31591580

Citations 415

Authors

Bilal Cakir

Yangfei Xiang

Yoshiaki Tanaka

Mehmet H Kural

Maxime Parent

Young-Jin Kang

Kayley Chapeton

Benjamin Patterson

Yifan Yuan

Chang-Shun He

Micha Sam B Raredon

Jake Dengelegi

Kun-Yong Kim

Pingnan Sun

Mei Zhong

Sangho Lee

Prabir Patra

Fahmeed Hyder

Laura E Niklason

Sang-Hun Lee

Young-Sup Yoon

In-Hyun Park

Affiliations

Soon will be listed here.

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.

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