Mouse organoid culture is a suitable model to study esophageal ion transport mechanisms

• Published in: American Journal of Physiology: Cell Physiology 2021-11, Vol.321 (5), p.C798-C811
• Main Authors: Korsós, Marietta Margaréta, Bellák, Tamás, Becskeházi, Eszter, Gál, Eleonóra, Veréb, Zoltán, Hegyi, Péter, Venglovecz, Viktória
• Format: Article
• Language: English
• Subjects: Animals; Anoctamin-1 - genetics; Anoctamin-1 - metabolism; Antiporters - genetics; Antiporters - metabolism; Cell culture; Cell Culture Techniques; Cells, Cultured; Chloride-Bicarbonate Antiporters - genetics; Chloride-Bicarbonate Antiporters - metabolism; Cystic fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Epithelial cells; Epithelial Cells - metabolism; Esophageal diseases; Esophagus; Esophagus - cytology; Esophagus - metabolism; Female; Flow cytometry; Ion Transport; Ions; Male; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Mice; Mice, Inbred C57BL; Na+/H+-exchanging ATPase; Organoids; Organoids - cytology; Organoids - metabolism; Sodium-Bicarbonate Symporters - genetics; Sodium-Bicarbonate Symporters - metabolism; Sodium-Hydrogen Exchangers - genetics; Sodium-Hydrogen Exchangers - metabolism; Stem cell transplantation; Stem cells; Stem Cells - metabolism; Sulfate Transporters - genetics; Sulfate Transporters - metabolism
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00295.2021

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 three-dimensional (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 were generated from epithelial stem cells as shown by FACS analysis. Using conventional PCR and immunostaining, the presence of Slc26a6 Cl /HCO anion exchanger (AE), Na /H exchanger (NHE), Na /HCO cotransporter (NBC), cystic fibrosis transmembrane conductance regulator (CFTR), and anoctamin 1 Cl channels was 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.