Electric Cell-Substrate Impedance Sensing (ECIS) as a Platform for Evaluating Barrier-Function Susceptibility and Damage from Pulmonary Atelectrauma.

Electric Cell-Substrate Impedance Sensing (ECIS) as a Platform for Evaluating Barrier-Function Susceptibility and Damage from Pulmonary Atelectrauma.
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DOI:
10.3390/bios12060390
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发表时间:
2022-06-05
期刊:
影响因子:
5.4
通讯作者:
Gaver, Donald P.
Gaver, Donald P.
中科院分区:
工程技术3区
文献类型:
--
作者:
Yamaguchi, Eiichiro;Yao, Joshua;Aymond, Allison;Chrisey, Douglas B.;Nieman, Gary F.;Bates, Jason H. T.;Gaver, Donald P.

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降低屏障功能(COVID-19、烟雾吸入、误吸和炎症)或增加机械应力(表面活性物质功能障碍)的生物物理损伤使肺部更容易发生肺不张损伤。我们研究了急性呼吸窘迫综合征(ARDS)和呼吸机诱导的肺损伤(VILI)中上皮细胞肺不电损伤相关屏障功能的易感性和时间依赖性破坏。本体外研究采用细胞-基质阻抗传感(ECIS)作为一种无创评估技术,对人肺上皮细胞系NCI-H441单层细胞进行重复性应激刺激/反应。通过向流体堵塞的微通道注入半无限气泡来模拟不电损伤。我们表明,具有高水平屏障功能的融合单层几乎不受数百例RD事件的电创伤影响。然而,屏障功能最终会减弱,经过一定数量的RD损伤后,单层会呈指数级分解。初始势垒函数较低的汇合层弹性较差。这些结果表明,不电损伤的第一道防线存在于细胞间结合。破坏后,上皮层群落保护减弱,继之而来的是不触电损伤。ECIS可以为识别损伤性刺激、通气场景或药物提供平台,这些药物可以降低易感性或增强屏障功能恢复。
Biophysical insults that either reduce barrier function (COVID-19, smoke inhalation, aspiration, and inflammation) or increase mechanical stress (surfactant dysfunction) make the lung more susceptible to atelectrauma. We investigate the susceptibility and time-dependent disruption of barrier function associated with pulmonary atelectrauma of epithelial cells that occurs in acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). This in vitro study was performed using Electric Cell-substrate Impedance Sensing (ECIS) as a noninvasive evaluating technique for repetitive stress stimulus/response on monolayers of the human lung epithelial cell line NCI-H441. Atelectrauma was mimicked through recruitment/derecruitment (RD) of a semi-infinite air bubble to the fluid-occluded micro-channel. We show that a confluent monolayer with a high level of barrier function is nearly impervious to atelectrauma for hundreds of RD events. Nevertheless, barrier function is eventually diminished, and after a critical number of RD insults, the monolayer disintegrates exponentially. Confluent layers with lower initial barrier function are less resilient. These results indicate that the first line of defense from atelectrauma resides with intercellular binding. After disruption, the epithelial layer community protection is diminished and atelectrauma ensues. ECIS may provide a platform for identifying damaging stimuli, ventilation scenarios, or pharmaceuticals that can reduce susceptibility or enhance barrier-function recovery.
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