Pulmonary-arterial-hypertension (PAH)-on-a-chip: fabrication, validation and application.
Pulmonary-arterial-hypertension (PAH)-on-a-chip: fabrication, validation and application.
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DOI：
10.1039/d0lc00605j
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发表时间：
2020-09-21
期刊：
影响因子：
6.1
通讯作者：
Ahsan F
中科院分区：
文献类型：
--
作者：
Al-Hilal TA;Keshavarz A;Kadry H;Lahooti B;Al-Obaida A;Ding Z;Li W;Kamm R;McMurtry IF;Lahm T;Nozik-Grayck E;Stenmark KR;Ahsan F
目前用于肺动脉高压（PAH）的动物和细胞模型仅部分概括了其在人类中的病理生理，因此在再现该疾病的特征方面存在不足，在描绘性别差异方面不一致，并且不适合组合研究设计。在这里，我们试图在开发和验证人类多环芳烃的组织芯片模型中部署微工程的独创性。我们设计并制造了一个微流体装置来模拟肺动脉的管腔、内膜、内侧、外膜和血管周围层。通过培养三种类型的肺动脉细胞（PACs）——内皮细胞、平滑肌细胞和外膜细胞，我们在设备上重现了PAH的病理生理。病变（多环芳烃）PACs在芯片上生长时，会移出其指定的层，并产生与人类多环芳烃的主要病理相似的现象：内膜增厚、肌肉化和动脉重塑，并表现出内皮到间充质的转变。血流诱导的应激导致生长在芯片上的对照细胞发生形态变化并引发动脉重塑。我们的数据还表明，新开发的芯片可用于阐明PAH的性别差异，并研究现有和正在研究的抗PAH药物的治疗效果。我们相信这种小型装置可以用于测试关于人类多环芳烃病理生物学和药物治疗的各种流行的和新的假设。
Currently used animal and cellular models for pulmonary arterial hypertension (PAH) only partially recapitulate its pathophysiology in humans and are thus inadequate in reproducing the hallmarks of the disease, inconsistent in portraying the sex-disparity, and unyielding to combinatorial study designs. Here we sought to deploy the ingenuity of microengineering in developing and validating a tissue chip model for human PAH. We designed and fabricated a microfluidic device to emulate the luminal, intimal, medial, adventitial, and perivascular layers of a pulmonary artery. By growing three types of pulmonary arterial cells (PACs)-endothelial, smooth muscle, and adventitial cells, we recreated the PAH pathophysiology on the device. Diseased (PAH) PACs, when grown on the chips, moved of out their designated layers and created phenomena similar to the major pathologies of human PAH: intimal thickening, muscularization, and arterial remodeling and show an endothelial to mesenchymal transition. Flow-induced stress caused control cells, grown on the chips, to undergo morphological changes and elicit arterial remodeling. Our data also suggest that the newly developed chips can be used to elucidate the sex disparity in PAH and to study the therapeutic efficacy of existing and investigational anti-PAH drugs. We believe this miniaturized device can be deployed for testing various prevailing and new hypotheses regarding the pathobiology and drug therapy in human PAH.
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影响因子：
4.9
作者：
Rashid J;Nahar K;Raut S;Keshavarz A;Ahsan F
通讯作者：
Ahsan F
DOI：
10.1164/rccm.201607-1515pp
发表时间：
2017-03-01
影响因子：
24.7
作者：
Bonnet, Sebastien;Provencher, Steeve;Humbert, Marc
通讯作者：
Humbert, Marc
影响因子：
9.7
作者：
Ding, Yonghui;Xu, Xin;Tan, Wei
通讯作者：
Tan, Wei
DOI：
10.1164/rccm.201703-0502oc
发表时间：
2018-02-01
影响因子：
24.7
作者：
Budas, Grant R.;Boehm, Mario;Schermuly, Ralph T.
通讯作者：
Schermuly, Ralph T.
影响因子：
37.8
作者：
Hopper RK;Moonen JR;Diebold I;Cao A;Rhodes CJ;Tojais NF;Hennigs JK;Gu M;Wang L;Rabinovitch M
通讯作者：
Rabinovitch M