Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor
Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor
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DOI：
10.1063/1.4934713
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发表时间：
2015-09-01
期刊：
影响因子：
3.2
通讯作者：
Wikswo, John P.
中科院分区：
文献类型：
--
作者：
Brown, Jacquelyn A.;Pensabene, Virginia;Wikswo, John P.
血脑屏障（BBB）是一种关键结构，充当中枢神经系统与身体其他部分之间的“守门人”。血脑屏障负责促进所需营养物质进入大脑，并排除潜在的有害化合物；然而，这种复杂结构在体外一直难以精确模拟。准确的体外模型对于理解血脑屏障如何形成和发挥作用，以及评估药物和毒素穿过屏障的渗透情况是必要的。许多先前的模型未能支持参与血脑屏障形成的所有细胞类型，并且/或者缺乏成熟紧密连接形成所需的由流动产生的剪切力。为了解决这些问题并帮助建立一个更精确的血脑屏障体外模型，我们设计并制造了一种微流控装置，该装置由一个血管腔室和一个脑腔室组成，二者由一个多孔膜隔开。这种设计允许内皮细胞、星形胶质细胞和周细胞之间进行细胞间通讯，并对由膜隔开的两个腔室进行独立灌注。这个神经血管单元（NVU）大约相当于人脑的百万分之一，因此具有足够的细胞量来支持广泛的分析测量。神经血管单元已通过异硫氰酸荧光素（FITC） - 葡聚糖扩散和跨内皮电阻进行了验证。神经血管单元能够使用所有人类细胞类型对血脑屏障进行体外建模，并从屏障两侧采集流出物。（C）2015作者。除另有说明外，所有文章内容均根据知识共享署名3.0未本地化版本许可授权。
The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flowcreated shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier. (C) 2015 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.