RT Journal Article
SR Electronic
T1 Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201857
DO 10.26508/lsa.202201857
VO 6
IS 6
A1 Birimberg-Schwartz, Liron
A1 Ip, Wan
A1 Bartlett, Claire
A1 Avolio, Julie
A1 Vonk, Annelotte M
A1 Gunawardena, Tarini
A1 Du, Kai
A1 Esmaeili, Mohsen
A1 Beekman, Jeffrey M
A1 Rommens, Johanna
A1 Strug, Lisa
A1 Bear, Christine E
A1 Moraes, Theo J
A1 Gonska, Tanja
YR 2023
UL https://www.life-science-alliance.org/content/6/6/e202201857.abstract
AB Highly effective drugs modulating the defective protein encoded by the CFTR gene have revolutionized cystic fibrosis (CF) therapy. Preclinical drug-testing on human nasal epithelial (HNE) cell cultures and 3-dimensional human intestinal organoids (3D HIO) are used to address patient-specific variation in drug response and to optimize individual treatment for people with CF. This study is the first to report comparable CFTR functional responses to CFTR modulator treatment among patients with different classes of CFTR gene variants using the three methods of 2D HIO, 3D HIO, and HNE. Furthermore, 2D HIO showed good correlation to clinical outcome markers. A larger measurable CFTR functional range and access to the apical membrane were identified as advantages of 2D HIO over HNE and 3D HIO, respectively. Our study thus expands the utility of 2D intestinal monolayers as a preclinical drug testing tool for CF.