Mouse pancreatic ductal organoid culture as a relevant model to study exocrine pancreatic ion secretion

Réka Molnár, Tamara Madácsy, Árpád Varga, Margit Németh, Xénia Katona, Marietta Görög, Brigitta Molnár, Júlia Fanczal, Zoltán Rakonczay, Péter Hegyi, Petra Pallagi, József Maléth

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Abstract

Pancreatic exocrine secretory processes are challenging to investigate on primary epithelial cells. Pancreatic organoid cultures may help to overcome shortcomings of the current models, however the ion secretory processes in pancreatic organoids—and therefore their physiological relevance or their utility in disease modeling—are not known. To answer these questions, we provide side-by-side comparison of gene expression, morphology, and function of epithelial cells in primary isolated pancreatic ducts and organoids. We used mouse pancreatic ductal fragments for experiments or were grown in Matrigel to obtain organoid cultures. Using PCR analysis we showed that gene expression of ion channels and transporters remarkably overlap in primary ductal cells and organoids. Morphological analysis with scanning electron microscopy revealed that pancreatic organoids form polarized monolayers with brush border on the apical membrane. Whereas the expression and localization of key proteins involved in ductal secretion (cystic fibrosis transmembrane conductance regulator, Na+/H+ exchanger 1 and electrogenic Na+/HCO3 cotransporter 1) are equivalent to the primary ductal fragments. Measurements of intracellular pH and Cl levels revealed no significant difference in the activities of the apical Cl/HCO3 exchange, or in the basolateral Na+ dependent HCO3 uptake. In summary we found that ion transport activities in the mouse pancreatic organoids are remarkably similar to those observed in freshly isolated primary ductal fragments. These results suggest that organoids can be suitable and robust model to study pancreatic ductal epithelial ion transport in health and diseases and facilitate drug development for secretory pancreatic disorders like cystic fibrosis, or chronic pancreatitis.

Original languageEnglish
Pages (from-to)84-97
Number of pages14
JournalLaboratory Investigation
Volume100
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Molnár, R., Madácsy, T., Varga, Á., Németh, M., Katona, X., Görög, M., Molnár, B., Fanczal, J., Rakonczay, Z., Hegyi, P., Pallagi, P., & Maléth, J. (2020). Mouse pancreatic ductal organoid culture as a relevant model to study exocrine pancreatic ion secretion. Laboratory Investigation, 100(1), 84-97. https://doi.org/10.1038/s41374-019-0300-3