Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
Pfizer, Cambridge, Massachusetts, USA.
Nat Methods. 2016 Feb;13(2):151-7. doi: 10.1038/nmeth.3697. Epub 2015 Dec 21.
Here we describe the development of a human lung 'small airway-on-a-chip' containing a differentiated, mucociliary bronchiolar epithelium and an underlying microvascular endothelium that experiences fluid flow, which allows for analysis of organ-level lung pathophysiology in vitro. Exposure of the epithelium to interleukin-13 (IL-13) reconstituted the goblet cell hyperplasia, cytokine hypersecretion and decreased ciliary function of asthmatics. Small airway chips lined with epithelial cells from individuals with chronic obstructive pulmonary disease recapitulated features of the disease such as selective cytokine hypersecretion, increased neutrophil recruitment and clinical exacerbation by exposure to viral and bacterial infections. With this robust in vitro method for modeling human lung inflammatory disorders, it is possible to detect synergistic effects of lung endothelium and epithelium on cytokine secretion, identify new biomarkers of disease exacerbation and measure responses to anti-inflammatory compounds that inhibit cytokine-induced recruitment of circulating neutrophils under flow.
在这里，我们描述了一种人类肺部“小气道芯片”的开发，该芯片包含分化的、黏液纤毛性的支气管上皮细胞和下方经历流体流动的微血管内皮细胞，这使得能够在体外分析器官水平的肺部病理生理学。将上皮细胞暴露于白细胞介素 13（IL-13）中，可重建哮喘患者的杯状细胞增生、细胞因子过度分泌和纤毛功能下降。用来自慢性阻塞性肺疾病患者的上皮细胞衬里的小气道芯片再现了该疾病的特征，例如选择性细胞因子过度分泌、增加的中性粒细胞募集以及通过暴露于病毒和细菌感染而导致的临床恶化。通过这种强大的体外方法来模拟人类肺部炎症性疾病，有可能检测到肺内皮细胞和上皮细胞对细胞因子分泌的协同作用，鉴定疾病恶化的新生物标志物，并测量对抑制细胞因子诱导的循环中性粒细胞募集的抗炎化合物的反应。
