Chronic pancreatitis patient-derived organoids reveal new paths to precision therapeutics.

ABSTRACT: Chronic pancreatitis (CP) affects ~3 million people worldwide, yet altering the course of 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 36 PDOs from patients with idiopathic, hereditary, and alcohol-related CP with 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 wildtype CFTR. Clinically available CFTR modulators stabilized mutant or wildtype CFTR, restored CFTR

SUBMITTER: Osorio-Vasquez V 

PROVIDER: S-EPMC12633304 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature