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Modeling Esophagitis Using Human Three-Dimensional Organotypic Culture System.

Dorottya Laczkó1, Fang Wang2, F Bradley Johnson3

  • 1Division of Gastroenterology, Department of Medicine and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; First Department of Medicine, University of Szeged, Szeged, Hungary.

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Three-dimensional organotypic tissue culture (OTC) models esophagitis, revealing immune cells drive esophageal inflammation and DNA damage. Antioxidant treatment reversed damage, highlighting OTC

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Area of Science:

  • Gastroenterology
  • Immunology
  • Tissue Engineering

Background:

  • Esophagitis affects 20% of the US population, stemming from various triggers like acid reflux and infections.
  • Inflammation in esophagitis is a risk factor for esophageal strictures, Barrett esophagus, and adenocarcinoma.
  • Existing animal and human models limit research into esophagitis pathophysiology.

Purpose of the Study:

  • To investigate the utility of three-dimensional organotypic tissue culture (OTC) for modeling esophagitis.
  • To understand the interactions between immune cells and the esophageal epithelium in an inflammatory context.
  • To characterize the molecular events underlying esophagitis using an in vitro platform.

Main Methods:

  • Human immune cells were cultured under OTC conditions to assess viability and cytokine response.
  • An acute inflammatory environment was induced in the OTC model.
  • Effects on the overlying esophageal epithelium, including cell proliferation, DNA damage, and response to antioxidant treatment, were analyzed.

Main Results:

  • Human immune cells remained viable and responsive to cytokines within the OTC model.
  • Induced inflammation significantly impacted the esophageal epithelium, causing increased cell proliferation and hyperplasia.
  • Oxidative stress from inflammation led to DNA damage, which was reversible with antioxidant treatment.

Conclusions:

  • Immune cell-mediated injury is crucial in the pathogenesis of esophagitis.
  • The OTC platform effectively models esophagitis, enabling characterization of immune cell-epithelial interactions.
  • This model provides a valuable tool for studying the molecular mechanisms of esophagitis and potential therapeutic interventions.