Background: New functional assays using primary human intestinal adult stem cell cultures can be valuable tools to study epithelial defects in human diseases such as cystic fibrosis. Methods: CFTR-mediated ion transport was measured in rectal organoid-derived monolayers grown from subjects with various CFTR mutations and compared to donor-matched intestinal current measurements (ICM) in rectal biopsies and forskolin-induced swelling of rectal organoids. Results: Rectal organoid-derived monolayers were generated within four days. Ion transport measurements of CFTR function using these monolayers correlated with ICM and organoid swelling (r = 0.73 and 0.79 respectively). Culturing the monolayers under differentiation conditions enhanced the detection of mucus-secreting cells and was accompanied by reduced CFTR function. Conclusions: CFTR-dependent intestinal epithelial ion transport properties can be measured in rectal organoid-derived monolayers of subjects and correlate with donor-matched ICM and rectal organoid swelling.

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Keywords Biopsies, CFTR, Differentiation, Donor-matched, Electrophysiology, Monolayers, Organoids
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Journal Journal of Cystic Fibrosis
Zomer-van Ommen, D.D, de Poel, E. (Eyleen), Kruisselbrink, E, Oppelaar, H. (Hugo), Vonk, A.M, Janssens, H.M, … Beekman, J. (2018). Comparison of ex vivo and in vitro intestinal cystic fibrosis models to measure CFTR-dependent ion channel activity. Journal of Cystic Fibrosis. doi:10.1016/j.jcf.2018.02.007