TY - JOUR
T1 - Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia
AU - Amatngalim, Gimano D.
AU - Rodenburg, Lisa W.
AU - Aalbers, Bente L.
AU - Raeven, Henriette Hm
AU - Aarts, Ellen M.
AU - Sarhane, Dounia
AU - Spelier, Sacha
AU - Lefferts, Juliet W.
AU - Silva, Iris Al
AU - Nijenhuis, Wilco
AU - Vrendenbarg, Sacha
AU - Kruisselbrink, Evelien
AU - Brunsveld, Jesse E.
AU - van Drunen, Cornelis M.
AU - Michel, Sabine
AU - de Winter-de Groot, Karin M.
AU - Heijerman, Harry G.
AU - Kapitein, Lukas C.
AU - Amaral, Magarida D.
AU - van der Ent, Cornelis K.
AU - Beekman, Jeffrey M.
N1 - 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.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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-1β and interleukin-1β, which enabled consistent detection of CFTR modulator responses in nasal-airway organoid cultures from subjects with cystic fibrosis.
AB - 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-1β and interleukin-1β, which enabled consistent detection of CFTR modulator responses in nasal-airway organoid cultures from subjects with cystic fibrosis.
UR - http://www.scopus.com/inward/record.url?scp=85135501100&partnerID=8YFLogxK
U2 - https://doi.org/10.26508/lsa.202101320
DO - https://doi.org/10.26508/lsa.202101320
M3 - Article
C2 - 35922154
SN - 2575-1077
VL - 5
JO - Life Science Alliance
JF - Life Science Alliance
IS - 12
M1 - e202101320
ER -