TY - JOUR
T1 - Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis
AU - Birimberg-Schwartz, Liron
AU - Ip, Wan
AU - Bartlett, Claire
AU - Avolio, Julie
AU - Vonk, Annelotte M.
AU - Gunawardena, Tarini
AU - Du, Kai
AU - Esmaeili, Mohsen
AU - Beekman, Jeffrey M.
AU - Rommens, Johanna
AU - Strug, Lisa
AU - Bear, Christine E.
AU - Moraes, Theo J.
AU - Gonska, Tanja
N1 - Funding Information:
T Gunawardena performed consultation service for Vertex Pharmaceuticals. T Gonska received funding from Vertex Pharmaceuticals for an investigator-initiated study and from AbbVie as part of a collaborative research project.
Publisher Copyright:
© 2023 Birimberg-Schwartz et al.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85151820134&partnerID=8YFLogxK
U2 - 10.26508/lsa.202201857
DO - 10.26508/lsa.202201857
M3 - Article
C2 - 37024122
AN - SCOPUS:85151820134
VL - 6
JO - Life Science Alliance
JF - Life Science Alliance
IS - 6
M1 - e202201857
ER -