Evidence map›Paper›PMID 37349353›Full record

ArticleScientific reports2023

Development of a novel air-liquid interface airway tissue equivalent model for in vitro respiratory modeling studies.

Timothy Leach, Uma Gandhi, Kimberly D Reeves, Kristina Stumpf, Kenichi Okuda, Frank C Marini, Stephen J Walker, Richard Boucher, Jeannie Chan, Laura A Cox and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

54 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Preclinical models of COPD: a state of the art review.The European respiratory journal · 2026
    Review
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  5. Review
  6. Review
  7. Preclinical human models of primary ciliary dyskinesia.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. A human airway-on-a-chip microphysiological system for modeling chlorine gas toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2026
    Article
  15. Article
  16. Article
  17. Article
  18. Loss of PIK3CA allowsbioRxiv : the preprint server for biology · 2026
    Article
  19. Article
  20. Article
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

12 authors at 4 institutions in 1 country.

Timothy LeachWake Forest School of Medicine, Medical Center, Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.
Uma GandhiWake Forest School of Medicine, Medical Center, Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.
Kimberly D ReevesCenter for Precision Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Kristina StumpfWake Forest School of Medicine, Medical Center, Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.
Kenichi OkudaMarsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Frank C MariniWake Forest School of Medicine, Medical Center, Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.
Stephen J WalkerWake Forest School of Medicine, Medical Center, Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.ORCID 0000-0002-0732-2366
Richard BoucherMarsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Jeannie ChanCenter for Precision Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
Laura A CoxCenter for Precision Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.ORCID 0000-0002-8836-3783
Anthony AtalaWake Forest School of Medicine, Medical Center, Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.ORCID 0000-0001-8186-2160
Sean V MurphyWake Forest School of Medicine, Medical Center, Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA. semurphy@wakehealth.edu.ORCID 0000-0002-2820-2451
Forest Institute · USWake Forest University · USUniversity of North Carolina at Chapel Hill · USVirginia Tech - Wake Forest University School of Biomedical Engineering & Sciences · US

Funding

Bioengineered Multi-Cell Type Organoids For Airways Disease ModelingR01HL143076 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI MURPHY, SEAN VINCENT · 2019 to 2021
$1.2M
NHLBI NIH HHS R01 HL143076
6 · The paper itself

Abstract

The human airways are complex structures with important interactions between cells, extracellular matrix (ECM) proteins and the biomechanical microenvironment. A robust, well-differentiated in vitro culture system that accurately models these interactions would provide a useful tool for studying normal and pathological airway biology. Here, we report the development and characterization of a physiologically relevant air-liquid interface (ALI) 3D airway 'organ tissue equivalent' (OTE) model with three novel features: native pulmonary fibroblasts, solubilized lung ECM, and hydrogel substrate with tunable stiffness and porosity. We demonstrate the versatility of the OTE model by evaluating the impact of these features on human bronchial epithelial (HBE) cell phenotype. Variations of this model were analyzed during 28 days of ALI culture by evaluating epithelial confluence, trans-epithelial electrical resistance, and epithelial phenotype via multispectral immuno-histochemistry and next-generation sequencing. Cultures that included both solubilized lung ECM and native pulmonary fibroblasts within the hydrogel substrate formed well-differentiated ALI cultures that maintained a barrier function and expressed mature epithelial markers relating to goblet, club, and ciliated cells. Modulation of hydrogel stiffness did not negatively impact HBE differentiation and could be a valuable variable to alter epithelial phenotype. This study highlights the feasibility and versatility of a 3D airway OTE model to model the multiple components of the human airway 3D microenvironment.

Indexed as

Epithelial CellsLungCells, CulturedExtracellular Matrix ProteinsHumansHydrogelsPhenotypeExtracellular Matrix ProteinsHydrogels

Identifiers

PMID37349353
PMCPMC10287689
OpenAlexW4381683970

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.