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

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-indu...

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Bibliographic Details
Published in:	Life science alliance Vol. 5; no. 12; p. e202101320
Main Authors:	Amatngalim, Gimano D, Rodenburg, Lisa W, Aalbers, Bente L, Raeven, Henriette Hm, Aarts, Ellen M, Sarhane, Dounia, Spelier, Sacha, Lefferts, Juliet W, Silva, Iris Al, Nijenhuis, Wilco, Vrendenbarg, Sacha, Kruisselbrink, Evelien, Brunsveld, Jesse E, van Drunen, Cornelis M, Michel, Sabine, de Winter-de Groot, Karin M, Heijerman, Harry G, Kapitein, Lukas C, Amaral, Magarida D, van der Ent, Cornelis K, Beekman, Jeffrey M
Format:	Journal Article
Language:	English
Published:	United States Life Science Alliance LLC 01-12-2022
Subjects:	Cells, Cultured Cystic Fibrosis - genetics Cystic Fibrosis Transmembrane Conductance Regulator - genetics Epithelial Cells Humans Methods Organoids
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2575-1077 2575-1077
DOI:	10.26508/lsa.202101320