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Nat Methods. 2016 Feb;13(2):151-7. doi: 10.1038/nmeth.3697. Epub 2015 Dec 21.

Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro.

Author information

1
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
2
Pfizer, Cambridge, Massachusetts, USA.
3
Merck Research Laboratories, Boston, Massachusetts, USA.
4
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.
5
Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA.
6
Harvard Medical School, Harvard University, Boston, Massachusetts, USA.

Abstract

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.

PMID:
26689262
DOI:
10.1038/nmeth.3697
[Indexed for MEDLINE]

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