Evidence map›Paper›PMID 26840431›Full record

ArticleAmerican journal of respiratory and critical care medicine2016

Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering.

Colin R Butler, Robert E Hynds, Kate H C Gowers, Dani Do Hyang Lee, James M Brown, Claire Crowley, Vitor H Teixeira, Claire M Smith, Luca Urbani, Nicholas J Hamilton and 7 more

Abstract read
In one paragraph

Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
17.2field-weighted citation impact, top 1% 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

129 citing papers in PubMed, 223 citations in OpenAlex.

  1. Article
  2. Article
  3. Preclinical human models of primary ciliary dyskinesia.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  4. Tracheal Tissue Engineering: Advances and Challenges.Bioengineering (Basel, Switzerland) · 2026
    Review
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69 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Colin R Butler1 Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.ORCID 0000-0003-4192-0519
Robert E Hynds1 Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.ORCID 0000-0002-2170-8791
Kate H C Gowers1 Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.
Dani Do Hyang Lee2 Respiratory, Critical Care, and Anesthesia, Institute of Child Health, University College London, London, United Kingdom.
James M Brown1 Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.
Claire Crowley3 Stem Cell and Regenerative Medicine Section, Great Ormond Street Hospital and UCL Institute of Child Health, London, United Kingdom.
Vitor H Teixeira1 Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.
Claire M Smith2 Respiratory, Critical Care, and Anesthesia, Institute of Child Health, University College London, London, United Kingdom.
Luca Urbani3 Stem Cell and Regenerative Medicine Section, Great Ormond Street Hospital and UCL Institute of Child Health, London, United Kingdom.
Nicholas J Hamilton1 Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.
Ricky M Thakrar1 Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.
Helen L Booth4 Department of Thoracic Medicine, University College London Hospitals, London, United Kingdom; and.
Martin A Birchall5 UCL Ear Institute, Royal National Throat, Nose and Ear Hospital, London, United Kingdom.
Paolo De Coppi3 Stem Cell and Regenerative Medicine Section, Great Ormond Street Hospital and UCL Institute of Child Health, London, United Kingdom.
Adam Giangreco1 Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.
Christopher O'Callaghan2 Respiratory, Critical Care, and Anesthesia, Institute of Child Health, University College London, London, United Kingdom.
Sam M Janes1 Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.ORCID 0000-0002-6634-5939
University College London · GBGreat Ormond Street Hospital · GBRoyal London Hospital · GBRoyal National Throat Nose and Ear Hospital · GB

Funding

Biotechnology and Biological Sciences Research CouncilDepartment of Health RP_2014-04-046Medical Research Council G1001539Medical Research Council MR/K026453/1Medical Research Council MR/L002000/1Wellcome TrustWellcome Trust WT091730AIA
6 · The paper itself

Abstract

rationaleStem cell-based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience demonstrates that restoration of mucociliary clearance in the lungs after transplantation of tissue-engineered grafts is critical, with preclinical studies showing that seeding scaffolds with autologous mucosa improves regeneration. High epithelial cell-seeding densities are required in regenerative medicine, and existing techniques are inadequate to achieve coverage of clinically suitable grafts.

objectivesTo define a scalable cell culture system to deliver airway epithelium to clinical grafts.

methodsHuman respiratory epithelial cells derived from endobronchial biopsies were cultured using a combination of mitotically inactivated fibroblasts and Rho-associated protein kinase (ROCK) inhibition using Y-27632 (3T3+Y). Cells were analyzed by immunofluorescence, quantitative polymerase chain reaction, and flow cytometry to assess airway stem cell marker expression. Karyotyping and multiplex ligation-dependent probe amplification were performed to assess cell safety. Differentiation capacity was tested in three-dimensional tracheospheres, organotypic cultures, air-liquid interface cultures, and an in vivo tracheal xenograft model. Ciliary function was assessed in air-liquid interface cultures. MEASUREMENTS AND MAIN

results3T3-J2 feeder cells and ROCK inhibition allowed rapid expansion of airway basal cells. These cells were capable of multipotent differentiation in vitro, generating both ciliated and goblet cell lineages. Cilia were functional with normal beat frequency and pattern. Cultured cells repopulated tracheal scaffolds in a heterotopic transplantation xenograft model.

conclusionsOur method generates large numbers of functional airway basal epithelial cells with the efficiency demanded by clinical transplantation, suggesting its suitability for use in tracheal reconstruction.

Indexed as

Cell DifferentiationCells, CulturedEpithelial CellsFlow CytometryFluorescent Antibody TechniqueHumansMucociliary ClearancePolymerase Chain ReactionRespiratory MucosaRespiratory Tract DiseasesStem CellsTissue Engineeringadult stem cellsepitheliumrespiratory mucosatissue engineeringtrachea

Identifiers

PMID26840431
PMCPMC5003214
OpenAlexW2260223112

What OpenQuestion holds

Textmetadata
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.