Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia

Gimano D Amatngalim, Lisa W Rodenburg, Bente L Aalbers, Henriette Hm Raeven, Ellen M Aarts, Dounia Sarhane, Sacha Spelier, Juliet W Lefferts, Iris Al Silva, Wilco Nijenhuis, Sacha Vrendenbarg, Evelien Kruisselbrink, Jesse E Brunsveld, Cornelis M van Drunen, Sabine Michel, Karin M de Winter-de Groot, Harry G Heijerman, Lukas C Kapitein, Magarida D Amaral, Cornelis K van der EntJeffrey M Beekman

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Cystic fibrosis is caused by genetic defects that impair the CFTR channel in airway epithelial cells. These defects may be overcome by specific CFTR modulating drugs, for which the efficacy can be predicted in a personalized manner using 3D nasal-brushing-derived airway organoids in a forskolin-induced swelling assay. Despite of this, previously described CFTR function assays in 3D airway organoids were not fully optimal, because of inefficient organoid differentiation and limited scalability. In this report, we therefore describe an alternative method of culturing nasal-brushing-derived airway organoids, which are created from an equally differentiated airway epithelial monolayer of a 2D air-liquid interface culture. In addition, we have defined organoid culture conditions, with the growth factor/cytokine combination neuregulin-1 β and interleukin-1 β, which enabled consistent detection of CFTR modulator responses in nasal-airway organoid cultures from subjects with cystic fibrosis.

Original languageEnglish
Article numbere202101320
Pages (from-to)1-14
JournalLife Science Alliance
Issue number12
Publication statusPublished - Dec 2022


  • Cells, Cultured
  • Cystic Fibrosis Transmembrane Conductance Regulator/genetics
  • Cystic Fibrosis/genetics
  • Epithelial Cells
  • Humans
  • Organoids


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