{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:00:51Z","timestamp":1789182051082,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T00:00:00Z","timestamp":1640476800000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The well\u2010established 3D organoid culture method enabled efficient expansion of cholangiocyte\u2010like cells from intrahepatic (IHBD) and extrahepatic bile duct (EHBD) tissue biopsies. The extensive expansion capacity of these organoids enables various applications, from cholangiocyte disease modelling to bile duct tissue engineering. Recent research demonstrated the feasibility of culturing cholangiocyte organoids from bile, which was minimal\u2010invasive collected via endoscopic retrograde pancreaticography (ERCP). However, a detailed analysis of these bile cholangiocyte organoids (BCOs) and the cellular region of origin was not yet demonstrated. In this study, we characterize BCOs and mirror them to the already established organoids initiated from IHBD\u2010 and EHBD\u2010tissue. We demonstrate successful organoid\u2010initiation from extrahepatic bile collected from gallbladder after resection and by ERCP or percutaneous transhepatic cholangiopathy from a variety of patients. BCOs initiated from these three sources of bile all show features similar to in vivo cholangiocytes. The regional\u2010specific characteristics of the BCOs are reflected by the exclusive expression of regional common bile duct genes (<jats:italic>HOXB2<\/jats:italic> and <jats:italic>HOXB3<\/jats:italic>) by ERCP\u2010derived BCOs and gallbladder\u2010derived BCOs expressing gallbladder\u2010specific genes. Moreover, BCOs have limited hepatocyte\u2010fate differentiation potential compared to intrahepatic cholangiocyte organoids. These results indicate that organoid\u2010initiating cells in bile are likely of local (extrahepatic) origin and are not of intrahepatic origin. Regarding the functionality of organoid initiating cells in bile, we demonstrate that BCOs efficiently repopulate decellularized EHBD scaffolds and restore the monolayer of cholangiocyte\u2010like cells in vitro. Bile samples obtained through minimally invasive procedures provide a safe and effective alternative source of cholangiocyte organoids. The shedding of (organoid\u2010initiating) cholangiocytes in bile provides a convenient source of organoids for regenerative medicine.<\/jats:p>","DOI":"10.1002\/ctm2.566","type":"journal-article","created":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T16:24:03Z","timestamp":1640535843000},"source":"Crossref","is-referenced-by-count":36,"title":["Cholangiocyte organoids from human bile retain a local phenotype and can repopulate bile ducts in vitro"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1278-6517","authenticated-orcid":false,"given":"Floris J. 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