A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells.
A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells.
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DOI：
10.1038/nbt.4226
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发表时间：
2018-10
影响因子：
46.9
通讯作者：
Parker, Kevin Kit
中科院分区：
文献类型：
--
作者：
Maoz, Ben M.;Herland, Anna;FitzGerald, Edward A.;Grevesse, Thomas;Vidoudez, Charles;Pacheco, Alan R.;Sheehy, Sean P.;Park, Tae-Eun;Dauth, Stephanie;Mannix, Robert;Budnik, Nikita;Shores, Kevin;Cho, Alexander;Nawroth, Janna C.;Segre, Daniel;Budnik, Bogdan;Ingber, Donald E.;Parker, Kevin Kit
神经血管单位（NVU）调节代谢稳态以及中枢神经系统中的药物药代动力学和药效学。NVU上的代谢通量和转化依赖于脑微血管内皮细胞、血管周细胞、星形胶质细胞和神经元之间的相互作用，使得难以识别每种细胞类型的贡献。在这里，我们使用微流控器官芯片对人类NVU进行建模，从而分析单个细胞类型在NVU功能中的作用。三个耦合芯片模拟了穿过血脑屏障（BBB）的流入、脑实质隔室和穿过BBB的流出。我们用这个连接系统来模拟血管内给药的精神活性药物甲基苯丙胺的效果，并确定以前未知的BBB和神经元之间的代谢耦合。因此，NVU系统提供了一种用于探测神经活性药物的转运、功效、作用机制和毒性的体外方法。
The neurovascular unit (NVU) regulates metabolic homeostasis as well as drug pharmacokinetics and pharmacodynamics in the central nervous system. Metabolic fluxes and conversions over the NVU rely on interactions between brain microvascular endothelium, perivascular pericytes, astrocytes and neurons, making it difficult to identify the contributions of each cell type. Here we model the human NVU using microfluidic organ chips, allowing analysis of the roles of individual cell types in NVU functions. Three coupled chips model influx across the blood–brain barrier (BBB), the brain parenchymal compartment and efflux across the BBB. We used this linked system to mimic the effect of intravascular administration of the psychoactive drug methamphetamine and to identify previously unknown metabolic coupling between the BBB and neurons. Thus, the NVU system offers an in vitro approach for probing transport, efficacy, mechanism of action and toxicity of neuroactive drugs.
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影响因子：
46.9
作者：
通讯作者：
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影响因子：
5.8
作者：
Eichler, GS;Huang, S;Ingber, DE
通讯作者：
Ingber, DE
影响因子：
2.4
作者：
Fujimoto, Yohei;Kitaichi, Kiyoyuki;Hasegawa, Takaaki
通讯作者：
Hasegawa, Takaaki
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3.2
作者：
Brown, Jacquelyn A.;Pensabene, Virginia;Wikswo, John P.
通讯作者：
Wikswo, John P.
影响因子：
46.9
作者：
Bhatia, Sangeeta N.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.