title: Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro.
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.
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: Kambez H
authors.initials: KH
authors.lastname: Benam
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: Remi
authors.initials: R
authors.lastname: Villenave
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Lucchesi
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Varone
authors.affiliation: Pfizer, Cambridge, Massachusetts, USA.
authors.forename: Cedric
authors.initials: C
authors.lastname: Hubeau
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, USA.
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Alves
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Salmon
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Ferrante
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.|Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Weaver
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bahinski
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
authors.forename: Geraldine A
authors.initials: GA
authors.lastname: Hamilton
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.|Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.|Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Harvard University, Boston, Massachusetts, USA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
mesh_terms: D004848:Epithelium / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D018793:Interleukin-13 / Q000494:pharmacology*; D056656:Lab-On-A-Chip Devices; D008171:Lung Diseases / Q000188:drug therapy* / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D018793:Interleukin-13