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科学家开发出具有血管的人脑类器官体
作者:小柯机器人 发布时间:2019/10/8 14:34:04

美国耶鲁大学医学院In-Hyun Park小组开发出具有功能性血管样系统的人脑类器官体。2019年10月7日,《自然—方法学》在线发表了这一成果。

研究人员工程化了人类胚胎干细胞(hESC),使其异位表达人类ETS变体2(ETV2)。人类皮质类器官(hCO)中表达ETV2的细胞有助于在hCO中形成复杂的血管样网络。重要的是,血管系统样结构的存在导致类器官的功能成熟性增强。研究人员发现血管化的hCO(vhCO)获得了几种血脑屏障特征,包括紧密连接蛋白、营养转运蛋白和跨内皮电阻表达的增加。最后,ETV2诱导的内皮支持体内灌注血管的形成。这些vhCO形成类似于产前早期大脑中血管系统的血管样结构,并且它们提供了一个有力的模型在体外研究脑部疾病。

据悉,源自hESC的hCO提供了一个用于研究复杂三维组织中的人类大脑发育和疾病平台。然而,目前的hCO缺乏微血管系统,导致向hCO最内层输送的氧气和养分有限。

附:英文原文

Title: Engineering of human brain organoids with a functional vascular-like system

Author: 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 

Issue&Volume: 7 October 2019

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.

DOI: 10.1038/s41592-019-0586-5

Source: https://www.nature.com/articles/s41592-019-0586-5

 

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:28.467
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex