Modeling Esophagitis Using Human Three-Dimensional Organotypic Culture System

Dorottya Laczkó, Fang Wang, F. Bradley Johnson, Nirag Jhala, András Rosztóczy, Gregory G. Ginsberg, Gary W. Falk, Anil K. Rustgi, John P. Lynch

Research output: Article

4 Citations (Scopus)

Abstract

Esophagitis, whether caused by acid reflux, allergic responses, graft-versus-host disease, drugs, or infections, is a common condition of the gastrointestinal tract affecting nearly 20% of the US population. The instigating agent typically triggers an inflammatory response. The resulting inflammation is a risk factor for the development of esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Research into the pathophysiology of these conditions has been limited by the availability of animal and human model systems. Three-dimensional organotypic tissue culture (OTC) is an innovative three-dimensional multicellular in vitro platform that recapitulates normal esophageal epithelial stratification and differentiation. We hypothesized that this platform can be used to model esophagitis to better understand the interactions between immune cells and the esophageal epithelium. We found that human immune cells remain viable and respond to cytokines when cultured under OTC conditions. The acute inflammatory environment induced in the OTC significantly affected the overlying epithelium, inducing a regenerative response marked by increased cell proliferation and epithelial hyperplasia. Moreover, oxidative stress from the acute inflammation induced DNA damage and strand breaks in epithelial cells, which could be reversed by antioxidant treatment. These findings support the importance of immune cell–mediated esophageal injury in esophagitis and confirms the utility of the OTC platform to characterize the underlying molecular events in esophagitis.

Original languageEnglish
Pages (from-to)1787-1799
Number of pages13
JournalAmerican Journal of Pathology
Volume187
Issue number8
DOIs
Publication statusPublished - aug. 2017

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Laczkó, D., Wang, F., Johnson, F. B., Jhala, N., Rosztóczy, A., Ginsberg, G. G., Falk, G. W., Rustgi, A. K., & Lynch, J. P. (2017). Modeling Esophagitis Using Human Three-Dimensional Organotypic Culture System. American Journal of Pathology, 187(8), 1787-1799. https://doi.org/10.1016/j.ajpath.2017.04.013