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

The small airway-on-a-chip allows the recapitulation of human lung pathophysiology in vitro and analysis of responses to drugs. Here we describe the development of a human lung 'small airway-on-a-chip' containing a differentiated, mucociliary bronchiolar epithelium and an underlying microv...

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Veröffentlicht in:Nature methods 2016-02, Vol.13 (2), p.151-157
Hauptverfasser: Benam, Kambez H, Villenave, Remi, Lucchesi, Carolina, Varone, Antonio, Hubeau, Cedric, Lee, Hyun-Hee, Alves, Stephen E, Salmon, Michael, Ferrante, Thomas C, Weaver, James C, Bahinski, Anthony, Hamilton, Geraldine A, Ingber, Donald E
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container_title Nature methods
container_volume 13
creator Benam, Kambez H
Villenave, Remi
Lucchesi, Carolina
Varone, Antonio
Hubeau, Cedric
Lee, Hyun-Hee
Alves, Stephen E
Salmon, Michael
Ferrante, Thomas C
Weaver, James C
Bahinski, Anthony
Hamilton, Geraldine A
Ingber, Donald E
description The small airway-on-a-chip allows the recapitulation of human lung pathophysiology in vitro and analysis of responses to drugs. 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.
doi_str_mv 10.1038/nmeth.3697
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subjects 13
13/1
13/106
13/107
13/21
13/31
13/51
13/62
14
14/19
14/28
14/34
14/63
631/1647/277
631/250/127
631/443/1784
692/308/575
Analysis
Asthma
Bacterial diseases
Bioinformatics
Biological Microscopy
Biological Techniques
Biomedical Engineering/Biotechnology
Care and treatment
Chronic obstructive pulmonary disease
Drug metabolism
Drugs
Epithelium - drug effects
Humans
Immune response
Inflammation
Inflammation - metabolism
Inflammation - pathology
Interleukin-13 - pharmacology
Lab-On-A-Chip Devices
Life Sciences
Lung Diseases - drug therapy
Lung Diseases - metabolism
Lungs
Observations
Pathology
Physiology
Proteomics
Regulation
Synergistic effect
Tissue Culture Techniques
title Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro
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