Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia
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
(2022) Life Science Alliance, volume 5, issue 12, pp. 1 - 14
(Article)
Abstract
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,
... read more
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.
show less
Download/Full Text
Keywords: Cells, Cultured, Cystic Fibrosis Transmembrane Conductance Regulator/genetics, Cystic Fibrosis/genetics, Epithelial Cells, Humans, Organoids, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 2575-1077
Publisher: Rockefeller University Press
Note: Funding Information: This work was supported by grants of the Dutch Cystic Fibrosis Foundation (NCFS, HIT-CF grant); the Netherlands Organization for Health Research and Development (ZonMw); Health Holland (grant no 40-41200-98-9296); SRC 013 from CF Trust-UK; UIDB/04046/2020 and UIDP/04046/2020 center grants (to BioISI), both from FCT/MCTES Portugal; and “HIT-CF” (H2020-SC1-2017-755021) from the EU. This work is supported by the European Research Council (ERC Consolidator Grant 819219 to LC Kapitein). Publisher Copyright: © 2022 Amatngalim et al.
(Peer reviewed)