A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources.
A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources.
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DOI：
10.1038/srep04160
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发表时间：
2014-02-24
影响因子：
4.6
通讯作者：
Shusta EV
中科院分区：
文献类型：
--
作者：
Lippmann ES;Al-Ahmad A;Azarin SM;Palecek SP;Shusta EV
血脑屏障（BBB）模型常用于研究BBB功能和筛选脑穿透治疗剂，但一直难以构建具有最佳BBB表型且易于扩展的人类模型。为了解决这一挑战，我们开发了一种人体外BBB模型，其包含脑微血管内皮细胞（BMEC）、周细胞、星形胶质细胞和源自可再生细胞来源的神经元。首先，视黄酸（RA）用于显著增强人多能干细胞（hPSC）衍生的BMEC中的BBB表型，特别是通过粘附连接、紧密连接和多药耐药蛋白调节。随后将RA处理的hPSC衍生的BMEC与原代人脑周细胞和人星形胶质细胞以及衍生自人神经祖细胞（NPC）的神经元共培养，以产生完全人BBB模型，其具有显著的紧密性，如通过跨内皮电阻（~ 5，000 Ω xcm 2）所测量的。 总的来说，这种可扩展的人类BBB模型可以实现广泛的神经科学研究。
Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm2). Overall, this scalable human BBB model may enable a wide range of neuroscience studies.
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影响因子：
16.2
作者：
Liu, JP;Laufer, E;Jessell, TM
通讯作者：
Jessell, TM
影响因子：
9.2
作者：
Maden, M;Gale, E;Zile, M
通讯作者：
Zile, M
使用干细胞来源模拟血脑屏障。
影响因子：
7.3
作者：
Lippmann ES;Al-Ahmad A;Palecek SP;Shusta EV
通讯作者：
Shusta EV
影响因子：
3.7
作者：
Daneman R;Zhou L;Agalliu D;Cahoy JD;Kaushal A;Barres BA
通讯作者：
Barres BA
影响因子：
4.7
作者：
Durk MR;Chan GN;Campos CR;Peart JC;Chow EC;Lee E;Cannon RE;Bendayan R;Miller DS;Pang KS
通讯作者：
Pang KS