Evidence map›Paper›PMID 25093641›Full record

ArticleLab on a chip2014

Human airway musculature on a chip: an in vitro model of allergic asthmatic bronchoconstriction and bronchodilation.

Alexander Peyton Nesmith, Ashutosh Agarwal, Megan Laura McCain, Kevin Kit Parker

Abstract read
In one paragraph

Article in Lab on a chip, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 91 citations in OpenAlex.

  1. Review
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  8. Microphysiological systems to advance human pathophysiology and translational medicine.Journal of applied physiology (Bethesda, Md. : 1985) · 2024
    Review
  9. Article
  10. Review
  11. Advancements in preclinical human-relevant modeling of pulmonary vasculature on-chip.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2024
    Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Engineering and Modeling the Lung Mesenchyme.Advances in experimental medicine and biology · 2023
    Article
  20. Human microphysiological models of airway and alveolar epithelia.American journal of physiology. Lung cellular and molecular physiology · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Alexander Peyton NesmithDisease Biophysics Group, Wyss Institute for Biologically Inspired Engineering and the School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Pierce Hall 321, Cambridge, MA 02138, USA. kkparker@seas.harvard.edu.
Ashutosh Agarwal
Megan Laura McCain
Kevin Kit Parker
Harvard University · US

Funding

PROMYELOCYTIC LEUKEMIA PROTEINS ROLE IN APOPTOSISR01CA080728 · NCI · UNIVERSITY OF MONTREAL · PI KATHERINE L B BORDEN · 1999 to 2026
$5.3M
Human Cardio-Pulmonary System on a ChipUH3TR000522 · NCATS · HARVARD MEDICAL SCHOOL · PI PARKER, KEVIN KIT · 2014 to 2016
$3.6M
Human Cardio-Pulmonary System on a ChipUH2TR000522 · NCATS · HARVARD MEDICAL SCHOOL · PI PARKER, KEVIN KIT · 2012 to 2013
$2.4M
NCATS NIH HHS UH3 TR000522NCI NIH HHS R01 CA080728NINDS NIH HHS UH2 NS080728-01
6 · The paper itself

Abstract

Many potential new asthma therapies that show promise in the pre-clinical stage of drug development do not demonstrate efficacy during clinical trials. One factor contributing to this problem is the lack of human-relevant models of the airway that recapitulate the tissue-level structural and functional phenotypes of asthma. Hence, we sought to build a model of a human airway musculature on a chip that simulates healthy and asthmatic bronchoconstriction and bronchodilation in vitro by engineering anisotropic, laminar bronchial smooth muscle tissue on elastomeric thin films. In response to a cholinergic agonist, the muscle layer contracts and induces thin film bending, which serves as an in vitro analogue for bronchoconstriction. To mimic asthmatic inflammation, we exposed the engineered tissues to interleukin-13, which resulted in hypercontractility and altered relaxation in response to cholinergic challenge, similar to responses observed clinically in asthmatic patients as well as in studies with animal tissue. Moreover, we reversed asthmatic hypercontraction using a muscarinic antagonist and a β-agonist which are used clinically to relax constricted airways. Importantly, we demonstrated that targeting RhoA-mediated contraction using HA1077 decreased basal tone, prevented hypercontraction, and improved relaxation of the engineered tissues exposed to IL-13. These data suggest that we can recapitulate the structural and functional hallmarks of human asthmatic musculature on a chip, including responses to drug treatments for evaluation of safety and efficacy of new drugs. Further, our airway musculature on a chip provides an important tool for enabling mechanism-based search for new therapeutic targets through the ability to evaluate engineered muscle at the levels of protein expression, tissue structure, and tissue function.

Indexed as

BronchoconstrictionLab-On-A-Chip DevicesModels, BiologicalMuscle, SmoothAsthmaBronchodilator AgentsCells, CulturedDrug Evaluation, PreclinicalGlassHumansProtein Kinase Inhibitorsrho-Associated KinasesBronchodilator AgentsProtein Kinase Inhibitorsrho-Associated Kinases

Identifiers

PMID25093641
PMCPMC4167568
OpenAlexW2167755652

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.