Vascularized liver-on-a-chip model to investigate nicotine-induced dysfunction.
Vascularized liver-on-a-chip model to investigate nicotine-induced dysfunction.
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DOI：
10.1063/5.0172677
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发表时间：
2023-12
期刊：
影响因子：
3.2
通讯作者：
Smith, Quinton
中科院分区：
文献类型：
--
作者：
Wang, Eric;Andrade, Melisa J.;Smith, Quinton
开发与生理相关的体外系统来模拟疾病的发生和发展，预测药物代谢，对于减少药物发现时间和成本具有巨大的价值。然而，这些平台中的许多在复制组织结构和多细胞相互作用方面缺乏准确性。通过利用三维细胞培养、仿生软水凝胶和工程刺激，体外模型继续取得进展。然而，微血管系统的结合遇到了许多挑战，特别是在增加实质细胞类型的情况下。在这里，采用一种系统的方法来研究内皮细胞的初始种植密度及其对互联网络的影响，并将其与肝脏球体结合形成芯片上的肝脏模型。利用这一系统，研究了尼古丁对微血管和肝功能的影响。结果表明，尼古丁导致黏附连接中断，鸟苷三磷酸环水解酶1表达降低，血管生成受损，屏障功能降低，这些都是内皮功能障碍的关键因素。在优化的微血管网络的结合下，形成了一个血管化的芯片上肝，提供了功能强大的异种代谢和白蛋白和尿素的合成。该系统提供了对各种药物引起的潜在肝毒性的洞察，并允许以高通量的方式评估血管功能障碍。
The development of physiologically relevant in vitro systems for simulating disease onset and progression and predicting drug metabolism holds tremendous value in reducing drug discovery time and cost. However, many of these platforms lack accuracy in replicating the tissue architecture and multicellular interactions. By leveraging three-dimensional cell culture, biomimetic soft hydrogels, and engineered stimuli, in vitro models have continued to progress. Nonetheless, the incorporation of the microvasculature has been met with many challenges, specifically with the addition of parenchymal cell types. Here, a systematic approach to investigating the initial seeding density of endothelial cells and its effects on interconnected networks was taken and combined with hepatic spheroids to form a liver-on-a-chip model. Leveraging this system, nicotine's effects on microvasculature and hepatic function were investigated. The findings indicated that nicotine led to interrupted adherens junctions, decreased guanosine triphosphate cyclohydrolase 1 expression, impaired angiogenesis, and lowered barrier function, all key factors in endothelial dysfunction. With the combination of the optimized microvascular networks, a vascularized liver-on-a-chip was formed, providing functional xenobiotic metabolism and synthesis of both albumin and urea. This system provides insight into potential hepatotoxicity caused by various drugs and allows for assessing vascular dysfunction in a high throughput manner.
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影响因子：
3.7
作者：
An N;Andrukhov O;Tang Y;Falkensammer F;Bantleon HP;Ouyang X;Rausch-Fan X
通讯作者：
Rausch-Fan X
影响因子：
3.7
作者：
Gori M;Simonelli MC;Giannitelli SM;Businaro L;Trombetta M;Rainer A
通讯作者：
Rainer A
DOI：
10.1161/atvbaha.112.252080
发表时间：
2012-08-01
影响因子：
8.7
作者：
Fernandez-Martin, Laura;Marcos-Ramiro, Beatriz;Millan, Jaime
通讯作者：
Millan, Jaime
影响因子：
4
作者：
Fong, Lai Yen;Ng, Chin Theng;Ahmad, Zuraini
通讯作者：
Ahmad, Zuraini
影响因子：
23.9
作者：
Gage, Blair K.;Liu, Jeff C.;Keller, Gordon M.
通讯作者：
Keller, Gordon M.