{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:28:57Z","timestamp":1792672137089,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T00:00:00Z","timestamp":1552435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T00:00:00Z","timestamp":1552435200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:p>\n                    Primary sclerosing cholangitis (PSC) is a heterogeneous and progressive fibroinflammatory cholangiopathy with no known etiology or effective treatment. Studies of PSC are limited due to difficulty in accessing the cholangiocyte, the small percentage of these cells in the liver, instability of\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    culture systems, and reliance on samples from end\u2010stage disease. Here, we demonstrate that stem cells can be isolated from the bile of PSC patients undergoing endoscopic retrograde cholangiopancreatography earlier in their clinical course and maintained long term\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    as three\u2010dimensional (3D) organoids that express a biliary genetic phenotype. Additionally, bile\u2010derived organoids (BDOs) can be biobanked and samples obtained longitudinally over the course of the disease. These BDOs express known cholangiocyte markers including gamma glutamyl transferase, cytokeratin 19, epithelial cellular adhesion molecule, cystic fibrosis transmembrane conductance regulator, and anion exchanger 2. RNA sequence analysis identified 39 genes whose expression differed in organoids from PSC patients compared to non\u2010PSC controls, including human leukocyte antigen DM alpha chain and chemokine (C\u2010C motif) ligand 20 (CCL20), immune\u2010related genes previously described in genome\u2010wide association studies of PSC. Incubation of these BDOs with interleukin 17A or tumor necrosis factor alpha led to an immune\u2010reactive phenotype with a significant increase in secretion of proinflammatory mediators, including CCL20, a T\u2010cell chemoattractant.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : This study demonstrates that bile can be used as a source of biliary\u2010like cells that can be maintained long term\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    as 3D organoids; these BDOs retain features of cholangiopathies, including the ability to react to inflammatory stimuli by secreting chemokines and propagating an immune\u2010reactive phenotype reflective of the pathogenesis of these diseases; thus, BDOs represent a platform for the study of the pathogenesis and therapy of cholangiopathies, particularly PSC.\n                  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