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  • Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis.

Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis.

Life science alliance (2023-04-07)
Liron Birimberg-Schwartz, Wan Ip, Claire Bartlett, Julie Avolio, Annelotte M Vonk, Tarini Gunawardena, Kai Du, Mohsen Esmaeili, Jeffrey M Beekman, Johanna Rommens, Lisa Strug, Christine E Bear, Theo J Moraes, Tanja Gonska
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
G 418 disulfate salt solution, 50 mg/mL in H2O, 0.1 μm filtered, BioReagent, suitable for cell culture