Patient-derived organoids reveal ductal dysfunction and CFTR-modulator responses in chronic pancreatitis
Year: 2026
Type: article
Abstract: Chronic pancreatitis (CP) affects ∼3 million people worldwide, yet altering the course of the disease is challenging. We developed a patient-derived organoid (PDO) platform to investigate the molecular pathogenesis of this disease and identify therapeutic strategies. We generated 37 PDOs from patients with idiopathic, hereditary, and alcohol-related CP with a high genetic concordance. PDOs retained inflammation-associated transcriptional and proteomic features. Transcriptomic profiling revealed three molecular subtypes of CP independent of etiology. We discovered widespread dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) in half of the CP PDOs, including those with wild-type CFTR. Clinically available CFTR modulators stabilized mutant or wild-type CFTR, restored CFTR function, and decreased mitogenic and inflammatory signaling. This work provides a comprehensive PDO platform for modeling CP. We demonstrate the utility of this platform for precision therapeutic investigations. Our findings reveal CFTR modulators as a broadly applicable and effective therapeutic strategy.
Source: Cell stem cell
Authors: Victoria Osorio-Vasquez, Jonathan Zhu, Jan C. Lumibao, Kathryn Lande, Kristina L. Peck, McKenna K. Stamp, Shira R. Okhovat, Hyemin Song, Satoshi Ogawa, Casie S. Kubota, Vasiliki Pantazopoulou, Kassidy Curtis, Kahing Kuo, Yang Dai, Angelica Rock, Chelsea R. Bottomley, Ethan J. Thomas, Jasper Hsu, Araceli Herrera Morales, Alexandra Fowler, T’Onj McGriff, K. Garrett Evensen, April E. Williams, Siri Larsen, Muhamad Abdulla, Phil Greer, Jessica Gibson, Michael Downes, Ronald M. Evans, Andrew M. Lowy, David C. Whitcomb, Jingjing Zou, Alfredo Molinolo, Tae Gyu Oh, Rebekah R. White, Melena Bellin, Hervé Tiriac, Dannielle D. Engle
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Conrad Prebys Foundation, Mary K. Chapman Foundation, University of California, Lustgarten Foundation, Leona M. and Harry B. Helmsley Charitable Trust, Waitt Foundation, Newman Family Foundation, Paul M. Angell Family Foundation, National Institutes of Health, National Institute on Aging, National Cancer Institute, Alvah and Wyline Chapman Foundation
OpenAlex ID: W7166649344