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.
