title: Matched-Comparative Modeling of Normal and Diseased Human Airway Responses Using a Microengineered Breathing Lung Chip.
abstract: Smoking represents a major risk factor for chronic obstructive pulmonary disease (COPD), but it is difficult to characterize smoke-induced injury responses under physiological breathing conditions in humans due to patient-to-patient variability. Here, we show that a small airway-on-a-chip device lined by living human bronchiolar epithelium from normal or COPD patients can be connected to an instrument that "breathes" whole cigarette smoke in and out of the chips to study smoke-induced pathophysiology in vitro. This technology enables true matched comparisons of biological responses by culturing cells from the same individual with or without smoke exposure. These studies led to identification of ciliary micropathologies, COPD-specific molecular signatures, and epithelial responses to smoke generated by electronic cigarettes. The smoking airway-on-a-chip represents a tool to study normal and disease-specific responses of the human lung to inhaled smoke across molecular, cellular and tissue-level responses in an organ-relevant context.
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
authors.forename: Kambez H
authors.initials: KH
authors.lastname: Benam
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Novak
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02139, USA.
authors.forename: Janna
authors.initials: J
authors.lastname: Nawroth
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA; Vascular Biology Program, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Mariko
authors.initials: M
authors.lastname: Hirano-Kobayashi
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Ferrante
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: Choe
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Prantil-Baun
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02139, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Weaver
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bahinski
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02139, USA.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Parker
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02139, USA; Vascular Biology Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Surgery, Harvard Medical School, Boston, MA 02115, USA. Electronic address: don.ingber@wyss.harvard.edu.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
mesh_terms: D066300:Electronic Nicotine Delivery Systems; D004847:Epithelial Cells; D006801:Humans; D008168:Lung; D029424:Pulmonary Disease, Chronic Obstructive; D012119:Respiration; D012907:Smoking
keywords: biomarker; cell culture; cigarette smoke; cilia; cytokine; electronic cigarette; human study; lung airway; microfluidic; organ chip; transcriptomic analysis