Patient-Derived Organoids from Human Bile: An In Vitro Method to Study Cholangiopathies.

Abstract

Cholangiopathies, including primary sclerosing cholangitis, are a group of heterogeneous diseases characterized by inflammation and fibrosis of the intrahepatic and extrahepatic bile duct epithelium. Studies, especially of primary sclerosing cholangitis, have been hampered by the difficulty in accessing the cholangiocyte, instability of in vitro culture systems, and reliance on (limited) samples from end-stage disease. Here we describe a novel method of culturing biliary cells from bile of primary sclerosing cholangitis patients undergoing endoscopic retrograde cholangiopancreatography for clinical indications. These 3D organoid cultures demonstrate a biliary phenotype, can be maintained in vitro, and biobanked for future analyses. Given the need for diagnostic and therapeutic endoscopic retrograde cholangiopancreatography throughout the disease in many primary sclerosing cholangitis patients, this method can provide longitudinal studies in individual patients, allowing for a correlation of gene expression with disease status. These organoids can react to inflammatory stimuli, resulting in the secretion of chemo/cytokines indicative of the reactive immune phenotype characteristic of primary sclerosing cholangitis. Therefore, bile-derived organoids provide a model to study the pathogenesis and pharmacotherapeutic treatment of cholangiopathies.