Liron Birimberg-Schwartz - Validating organoid-derived human intestinal monolayers for personalized therapy in cystic fibrosis
Authors: 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 Bear, Theo J. Moraes, Tanja Gonska
Year of publication: 2023
Journal: Life Science Alliance
Abstract including results:
The advent of highly effective drugs that modulate the defective protein encoded by the CFTR gene has transformed cystic fibrosis (CF) therapy. Preclinical drug testing using human nasal epithelial (HNE) cell cultures and 3-dimensional human intestinal organoids (3D HIOs) is employed to address patient-specific variability in drug response and optimize individualized treatment for people with CF.
This study was the first to report comparable CFTR functional responses to modulator treatment across patients with different CFTR gene variants, utilizing three methodologies: 2D HIO, 3D HIO, and HNE cultures. Notably, 2D HIOs exhibited a strong correlation with clinical outcome markers. Additionally, 2D HIOs demonstrated a larger measurable CFTR functional range and better access to the apical membrane, offering advantages over HNE and 3D HIO models.
These findings underscore the potential of 2D intestinal monolayers as a robust preclinical drug testing tool for CF therapy.
Dr. Liron Birimberg-Schwartz, a Clinician-Scientist at Hadassah Medical Center, currently serves as the clinical director of the Hadassah Organoid Center. Building on her previous work, she continues to lead translational research initiatives that utilize intestinal organoids for personalized drug testing and treatment decisions in CF.