Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis.
Life Sci Alliance
; 6(6)2023 06.
Article
en En
| MEDLINE
| ID: mdl-37024122
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibrosis Quística
Límite:
Humans
Idioma:
En
Revista:
Life Sci Alliance
Año:
2023
Tipo del documento:
Article
País de afiliación:
Canadá