Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for Assessment of Therapeutics.
Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for Assessment of Therapeutics.
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DOI：
10.1002/cpt.742
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发表时间：
2018-03
影响因子：
6.7
通讯作者：
Ingber DE
中科院分区：
文献类型：
--
作者：
Jain A;Barrile R;van der Meer AD;Mammoto A;Mammoto T;De Ceunynck K;Aisiku O;Otieno MA;Louden CS;Hamilton GA;Flaumenhaft R;Ingber DE
肺血栓形成是导致患者死亡的重要原因，然而，还没有有效的人肺微血管中血栓形成的体外模型，其也可以评估抗血栓药物的治疗和毒理学。在这里，我们表明，一个微流控肺泡芯片内衬的人初级肺泡上皮细胞与内皮细胞，并培养下流动的全血可以用来进行定量分析器官水平的贡献炎症诱导的血栓形成。该微流控芯片概括了体内反应，包括血小板-内皮动力学，并揭示了脂多糖（LPS）内毒素通过激活肺泡上皮间接刺激血管内血栓形成，而不是直接作用于内皮。该模型还用于分析蛋白酶激活受体-1（PAR-1）拮抗剂对内皮激活和血栓形成的抑制，证明其能够剖析复杂的反应并识别抗血栓形成疗法。因此，这种方法学提供了一种新的方法来研究人类肺血栓形成的病理生理学和推进药物开发。
Pulmonary thrombosis is a significant cause of patient mortality, however, there are no effective in vitro models of thrombi formation in human lung microvessels, that could also assess therapeutics and toxicology of antithrombotic drugs. Here we show that a microfluidic lung alveolus-on-a-chip lined by human primary alveolar epithelium interfaced with endothelium, and cultured under flowing whole blood can be used to perform quantitative analysis of organ-level contributions to inflammation-induced thrombosis. This microfluidic chip recapitulates in vivo responses, including platelet-endothelial dynamics and revealed that lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis by activating the alveolar epithelium, rather than acting directly on endothelium. This model is also used to analyze inhibition of endothelial activation and thrombosis due to a protease activated receptor-1 (PAR-1) antagonist, demonstrating its ability to dissect complex responses and identify antithrombotic therapeutics. Thus, this methodology offers a new approach to study human pathophysiology of pulmonary thrombosis and advance drug development.
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影响因子：
3.8
作者：
Hansen, Ryan R.;Wufsus, Adam R.;Barton, Steven T.;Onasoga, Abimbola A.;Johnson-Paben, Rebecca M.;Neeves, Keith B.
通讯作者：
Neeves, Keith B.
DOI：
10.1161/atvbaha.111.225334
发表时间：
2011-06-01
影响因子：
8.7
作者：
Cooley, Brian C.
通讯作者：
Cooley, Brian C.
影响因子：
82.9
作者：
Falati, S;Gross, P;Furie, B
通讯作者：
Furie, B
DOI：
10.1126/science.1188302
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Huh D;Matthews BD;Mammoto A;Montoya-Zavala M;Hsin HY;Ingber DE
通讯作者：
Ingber DE
影响因子：
46.9
作者：
Bhatia, Sangeeta N.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.