Evidence map›Paper›PMID 28936470›Full record

ArticleCellular and molecular gastroenterology and hepatology2017

Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation.

Richard J von Furstenberg, Joy Li, Christina Stolarchuk, Rachel Feder, Alexa Campbell, Leandi Kruger, Liara M Gonzalez, Anthony T Blikslager, Diana M Cardona, Shannon J McCall and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

30 citing papers in PubMed, 41 citations in OpenAlex.

  1. Animal organoids as models for integrated One Health research.One health (Amsterdam, Netherlands) · 2026
    Review
  2. Pathogenesis of Barrett's Esophagus: Evolving and Emerging Mechanisms.Gastrointestinal endoscopy clinics of North America · 2026
    Review
  3. Article
  4. Epithelial architecture and signaling activity in the adult human esophagus.Frontiers in cell and developmental biology · 2025
    Review
  5. Article
  6. Cellular Origins and Lineage Plasticity in Cancer.Cold Spring Harbor perspectives in medicine · 2024
    Review
  7. Review
  8. Article
  9. Molecules involved in the development of Barrett's esophagus phenotype in chronic eosinophilic esophagitis.American journal of physiology. Gastrointestinal and liver physiology · 2022
    Article
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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 3 institutions in 1 country.

Richard J von FurstenbergDivision of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina.
Joy LiDivision of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina.
Christina StolarchukDivision of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina.
Rachel FederDivision of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina.
Alexa CampbellDivision of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina.
Leandi KrugerDepartment of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina.
Liara M GonzalezDepartment of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina.
Anthony T BlikslagerDepartment of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina.
Diana M CardonaDepartment of Pathology, Duke University, Durham, North Carolina.
Shannon J McCallDepartment of Pathology, Duke University, Durham, North Carolina.
Susan J HenningDivision of Gastroenterology, Department of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina.
Katherine S GarmanDivision of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina.
Duke University · USNorth Carolina State University · USUniversity of North Carolina at Chapel Hill · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI JOHN N. NORTON · 1985 to 2026
$174.8M
PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Temitope O. Keku · 1985 to 2026
$30.5M
Intestinal stem cell responses to ischemic injury in a large animal modelK01OD019911 · OD · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI GONZALEZ, LIARA M · 2015 to 2019
$608k
Submucosal esophageal structures as a progenitor niche for esophageal repairK08DK098528 · NIDDK · DUKE UNIVERSITY · PI GARMAN, KATHERINE · 2013 to 2017
$594k
NCI NIH HHS P30 CA014236NIDDK NIH HHS K08 DK098528NIDDK NIH HHS P30 DK034987NIH HHS K01 OD019911
6 · The paper itself

Abstract

BACKGROUND &

aimsAlthough cells comprising esophageal submucosal glands (ESMGs) represent a potential progenitor cell niche, new models are needed to understand their capacity to proliferate and differentiate. By histologic appearance, ESMGs have been associated with both overlying normal squamous epithelium and columnar epithelium. Our aim was to assess ESMG proliferation and differentiation in a 3-dimensional culture model.

methodsWe evaluated proliferation in human ESMGs from normal and diseased tissue by proliferating cell nuclear antigen immunohistochemistry. Next, we compared 5-ethynyl-2'-deoxyuridine labeling in porcine ESMGs in vivo before and after esophageal injury with a novel in vitro porcine organoid ESMG model. Microarray analysis of ESMGs in culture was compared with squamous epithelium and fresh ESMGs.

resultsMarked proliferation was observed in human ESMGs of diseased tissue. This activated ESMG state was recapitulated after esophageal injury in an in vivo porcine model, ESMGs assumed a ductal appearance with increased proliferation compared with control. Isolated and cultured porcine ESMGs produced buds with actively cycling cells and passaged to form epidermal growth factor-dependent spheroids. These spheroids were highly proliferative and were passaged multiple times. Two phenotypes of spheroids were identified: solid squamous (P63+) and hollow/ductal (cytokeratin 7+). Microarray analysis showed spheroids to be distinct from parent ESMGs and enriched for columnar transcripts.

conclusionsOur results suggest that the activated ESMG state, seen in both human disease and our porcine model, may provide a source of cells to repopulate damaged epithelium in a normal manner (squamous) or abnormally (columnar epithelium). This culture model will allow the evaluation of factors that drive ESMGs in the regeneration of injured epithelium. The raw microarray data have been uploaded to the National Center for Biotechnology Information Gene Expression Omnibus (accession number: GSE100543).

Indexed as

3D, 3-dimensional3D CultureAcinar Ductal MetaplasiaAdult Stem CellANOVA, analysis of varianceBarrett’s EsophagusBE, Barrett’s esophagusCK7, cytokeratin 7DMSO, dimethyl sulfoxideEAC, esophageal adenocarcinomaEdU, 5-ethynyl-2′-deoxyuridineEGF, epidermal growth factorESMG, esophageal submucosal glandEsophagusIHC, immunohistochemistryPBS, phosphate-buffered salinePCNA, proliferating cell nuclear antigenRFA, radiofrequency ablation

Identifiers

PMID28936470
PMCPMC5602779
OpenAlexW2743413726

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.