Neurovascular unit on a chip: implications for translational applications.
Neurovascular unit on a chip: implications for translational applications.
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DOI：
10.1186/scrt379
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发表时间：
2013
影响因子：
7.5
通讯作者：
Wikswo JP
中科院分区：
文献类型：
--
作者：
Alcendor DJ;Block FE 3rd;Cliffel DE;Daniels JS;Ellacott KL;Goodwin CR;Hofmeister LH;Li D;Markov DA;May JC;McCawley LJ;McLaughlin B;McLean JA;Niswender KD;Pensabene V;Seale KT;Sherrod SD;Sung HJ;Tabb DL;Webb DJ;Wikswo JP
血脑屏障（BBB）动态地控制大脑和身体之间的交换，但这种相互作用不能在完整的人脑中直接研究，也不能用动物模型充分代表。大多数现有的体外BBB模型不包括具有其他BBB元件的神经元和神经胶质，并且不能充分预测药物功效和毒性。在美国国立卫生研究院微组织倡议下，我们正在开发一种代表大脑神经血管单位的三维，多室，器官型微生理系统。神经血管单位系统将作为一个模型，研究中枢神经系统神经元和脑脊液（CSF）室之间的相互作用，所有耦合到一个现实的血液替代品供应和静脉回流系统，还包括循环免疫细胞和脉络丛。因此，将概括所有三个关键的脑屏障：血脑、脑CSF和血CSF。原代和干细胞衍生的人类细胞将与各种试剂相互作用，以产生跨越BBB和脑区域之间的关键化学通讯。巨细胞病毒是一种常见的疱疹病毒，将被用作由BBB调节的感染的初始模型。这个新的技术平台结合了创新的微流体，细胞培养，分析仪器，生物信息学，控制理论，神经科学和药物发现，将复制大脑中的化学通讯，分子运输和炎症。该平台将实现针对性和临床相关的营养和药理干预或预防肥胖和中风等急性损伤等慢性疾病，并将发现药物的潜在不良反应。如果成功，该项目将产生临床上有用的技术，并揭示大脑如何接收，修改和受药物，其他神经营养剂和疾病影响的新见解。
The blood-brain barrier (BBB) dynamically controls exchange between the brain and the body, but this interaction cannot be studied directly in the intact human brain or sufficiently represented by animal models. Most existing in vitro BBB models do not include neurons and glia with other BBB elements and do not adequately predict drug efficacy and toxicity. Under the National Institutes of Health Microtissue Initiative, we are developing a three-dimensional, multicompartment, organotypic microphysiological system representative of a neurovascular unit of the brain. The neurovascular unit system will serve as a model to study interactions between the central nervous system neurons and the cerebral spinal fluid (CSF) compartment, all coupled to a realistic blood-surrogate supply and venous return system that also incorporates circulating immune cells and the choroid plexus. Hence all three critical brain barriers will be recapitulated: blood-brain, brain-CSF, and blood-CSF. Primary and stem cell-derived human cells will interact with a variety of agents to produce critical chemical communications across the BBB and between brain regions. Cytomegalovirus, a common herpesvirus, will be used as an initial model of infections regulated by the BBB. This novel technological platform, which combines innovative microfluidics, cell culture, analytical instruments, bioinformatics, control theory, neuroscience, and drug discovery, will replicate chemical communication, molecular trafficking, and inflammation in the brain. The platform will enable targeted and clinically relevant nutritional and pharmacologic interventions for or prevention of such chronic diseases as obesity and acute injury such as stroke, and will uncover potential adverse effects of drugs. If successful, this project will produce clinically useful technologies and reveal new insights into how the brain receives, modifies, and is affected by drugs, other neurotropic agents, and diseases.
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