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新型三维生物芯片肺结节病模型。

Novel three-dimensional biochip pulmonary sarcoidosis model.

机构信息

Department of Medicine, University of Miami, Miami, FL, United States of America.

Division of Pulmonary and Critical Care, University of Miami, Miami, FL, United States of America.

出版信息

PLoS One. 2021 Feb 4;16(2):e0245805. doi: 10.1371/journal.pone.0245805. eCollection 2021.

Abstract

Sarcoidosis is a multi-system disorder of granulomatous inflammation which most commonly affects the lungs. Its etiology and pathogenesis are not well defined in part due to the lack of reliable modeling. Here, we present the development of an in vitro three-dimensional lung-on-chip biochip designed to mimic granuloma formation. A lung on chip fluidic macrodevice was developed and added to our previously developed a lung-on-membrane model (LOMM). Granulomas were cultured from blood samples of patients with sarcoidosis and then inserted in the air-lung-interface of the microchip to create a three-dimensional biochip pulmonary sarcoidosis model (3D BSGM). Cytokines were measured after 48 hours. ELISA testing was performed to measure cytokine response difference between LOMM with 3D BSGM. There were statistically significant differences in IL-1ß (P = 0.001953), IL-6 (P = 0.001953), GM-CSF (P = 0.001953), and INF-γ expressions (P = 0.09375) between two groups. The current model represents the first 3D biochip sarcoidosis model created by adding a microfluidics system to a dual-chambered lung on membrane model and introducing developed sarcoid-granuloma to its air-lung-interface.

摘要

结节病是一种多系统肉芽肿炎症性疾病,最常影响肺部。其病因和发病机制尚不完全清楚,部分原因是缺乏可靠的模型。在这里,我们介绍了一种体外三维肺芯片的开发,该芯片旨在模拟肉芽肿的形成。开发了一种肺芯片流体宏观器件,并将其添加到我们之前开发的肺膜模型(LOMM)中。从结节病患者的血液样本中培养出肉芽肿,然后将其插入微芯片的空气-肺界面,以创建三维生物芯片肺结节病模型(3D BSGM)。在 48 小时后测量细胞因子。通过 ELISA 测试测量 LOMM 和 3D BSGM 之间的细胞因子反应差异。两组之间的 IL-1ß(P = 0.001953)、IL-6(P = 0.001953)、GM-CSF(P = 0.001953)和 INF-γ 表达存在统计学显著差异(P = 0.09375)。当前的模型代表了第一个通过向双室肺膜模型添加微流控系统并将开发的结节肉芽肿引入其空气-肺界面来创建的 3D 生物芯片结节病模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2de3/7861546/e9155977a6d4/pone.0245805.g001.jpg

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