Journal
LIFE SCIENCE ALLIANCE
Volume 5, Issue 12, Pages -Publisher
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.202101320
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Funding
- Dutch Cystic Fibrosis Foundation (NCFS, HIT-CF grant)
- Netherlands Organization for Health Research and Development (ZonMw)
- Health Holland [40-41200-98-9296]
- CF Trust-UK [SRC 013]
- FCT/MCTES Portugal [UIDB/04046/2020, UIDP/04046/2020]
- EU [H2020-SC1-2017-755021]
- European Research Council (ERC) [819219]
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This study introduces an alternative method of culturing nasal-brushing-derived airway organoids, enabling consistent detection of CFTR modulator responses in patients with cystic fibrosis.
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 beta and interleukin-1 beta, which enabled consistent detection of CFTR modulator responses in nasal-airway organoid cultures from subjects with cystic fibrosis.
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