Cell Culture Models for Studying the Development of Barrett's Esophagus: a Systematic Review

Background: Barrett's esophagus (BE) is a premalignant condition caused by chronic gastroesophageal reflux. BE patients have an increased risk of developing esophageal adenocarcinoma (EAC). As many aspects of this condition are still unknown, there is a need for in vitro models to study BE development.

Aim: To review the literature on cell lines and incubation conditions for studying BE development.

Methods: A literature search was performed using PubMed, EMBASE and the Cochrane library, combining the words esophagus, cell line, culture, Barrett's, bile, acid, exposure, reflux and adenocarcinoma.

Results: A wide range of cell lines and incubation conditions to study BE development have been reported. The most commonly used cell lines are derived from epithelium from patients with BE or EAC. A 25-minute incubation with 200 μM bile salts induced cell proliferation and Akt phosphorylation. However, increased CDX2 and MUC2 expression was only observed with longer incubations or higher bile salt concentrations. Two-hundred μM bile at pH 6 showed a higher toxicity to EAC cells than the same concentration at pH 7. Multiple 5-minute exposures with 200 μM bile at pH 4 or pH 7 increased CK8/18 and COX2 in BE epithelial cells.

Conclusions: Two-hundred μM conjugated primary or secondary bile salts at pH 4 for multiple short exposures is able to induce BE specific factors in BE cell lines. In SQ and EAC cell lines; however, higher concentrations of secondary bile salts for 8 h are needed to induce BE specific molecules. Due to the high variability in reported methods, it is difficult to determine the most effective in vitro setup for studying the development of BE.