RT Journal Article
SR Electronic
T1 Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101320
DO 10.26508/lsa.202101320
VO 5
IS 12
A1 Amatngalim, Gimano D
A1 Rodenburg, Lisa W
A1 Aalbers, Bente L
A1 Raeven, Henriette HM
A1 Aarts, Ellen M
A1 Sarhane, Dounia
A1 Spelier, Sacha
A1 Lefferts, Juliet W
A1 Silva, Iris AL
A1 Nijenhuis, Wilco
A1 Vrendenbarg, Sacha
A1 Kruisselbrink, Evelien
A1 Brunsveld, Jesse E
A1 van Drunen, Cornelis M
A1 Michel, Sabine
A1 de Winter-de Groot, Karin M
A1 Heijerman, Harry G
A1 Kapitein, Lukas C
A1 Amaral, Magarida D
A1 van der Ent, Cornelis K
A1 Beekman, Jeffrey M
YR 2022
UL https://www.life-science-alliance.org/content/5/12/e202101320.abstract
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.