Altered esophageal ion transport mechanisms play a key role in inflammatory and cancerous
diseases of the esophagus, but epithelial ion processes have been less studied in
the esophagus because of the lack of a suitable experimental model. In this study,
we generated 3D esophageal organoids (EOs) from two different mouse strains and characterized
the ion transport processes of the EOs. EOs form a cell-filled structure with a diameter
of 250-300 µm and generated from epithelial stem cells as shown by FACS analysis.
Using conventional PCR and immunostaining, the presence of Slc26a6 Cl-/HCO3- anion
exchanger (AE), Na+/H+ exchanger (NHE), Na+/HCO3- cotransporter (NBC), cystic fibrosis
transmembrane conductance regulator (CFTR) and anoctamin 1 Cl- channels were detected
in EOs. Microfluorimetric techniques revealed high NHE, AE, and NBC activities, whereas
that of CFTR was relatively low. In addition, inhibition of CFTR led to functional
interactions between the major acid-base transporters and CFTR. We conclude that EOs
provide a relevant and suitable model system for studying the ion transport mechanisms
of esophageal epithelial cells, and they can be also used as preclinical tools to
assess the effectiveness of novel therapeutic compounds in esophageal diseases associated
with altered ion transport processes.