Cholangiocyte organoids from human bile retain a local phenotype and can repopulate bile ducts in vitro
Open accessAbstract
The well-established 3D organoid culture method enabled efficient expansion of cholangiocyte-like 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-invasive 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- and EHBD-tissue. We demonstrate successful organoid-initiation 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-specific characteristics of the BCOs are reflected by the exclusive expression of regional common bile duct genes (HOXB2 and HOXB3) by ERCP-derived BCOs and gallbladder-derived BCOs expressing gallbladder-specific genes. Moreover, BCOs have limited hepatocyte-fate differentiation potential compared to intrahepatic cholangiocyte organoids. These results indicate that organoid-initiating 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-like cells in vitro. Bile samples obtained through minimally invasive procedures provide a safe and effective alternative source of cholangiocyte organoids. The shedding of (organoid-initiating) cholangiocytes in bile provides a convenient source of organoids for regenerative medicine.
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Organoid technology shows great promise for regenerative medicine due to its ability to differentiate, self-organize, and proliferate in high and stable capacity without losing the desirable cholangiocyte phenotype.
“Recently, organoid technology has shown great promise for regenerative medicine due to its ability to differentiate, self-organize, and proliferate in high and stable capacity without losing the desirable cholangiocyte phenotype [248,249].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [249]
The Discussion (page not provided) reports long-term expansion of bile-derived cholangiocyte organoids without loss of morphological characteristics and identifies their potential for tissue engineering and regenerative medicine. The Results (page not provided) show that these organoids retain cholangiocyte-like properties, but have little to no ability to acquire hepatocyte-like properties. The source therefore supports proliferation and phenotype retention, but not an unqualified ability to differentiate; it does not explicitly establish self-organization as a reason for that promise. (LLM, conf=0.86)
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- Authors
- Roos, F. J. M., Wu, H., Willemse, J., Lieshout, R., Albarinos, L. A. M., Kan, Y., Poley, J., Bruno, M. J., de Jonge, J., Bártfai, R., Marks, H., IJzermans, J. N. M., Verstegen, M. M. A., & van der Laan, L. J. W.
- Affiliations
- Erasmus MC (NL)
- Radboud University Nijmegen (NL)
- Erasmus MC Department of Surgery, University Medical Center Rotterdam Rotterdam The Netherlands
- Department of Molecular Biology, Radboud University Nijmegen The Netherlands
- ORCID
- Venue
- Clinical and Translational Medicine
- Publisher
- Wiley
- Published
- 2021-12
- Volume
- 11
- Issue
- 12
- Pages
- e566-e566
- ISSN
- 2001-1326 (ISSN-L)
- PMC
- PMC8710298
- OpenAlex
- W4200354503
- Cited by
- 40
- References
- 52
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 14 · 2023: 4 · 2022: 5 · 2021: 1 · 2012: 1
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Clinical and Translational Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- cholangiocyte organoids, bile, extrahepatic bile ducts, gallbladder, endoscopic retrograde cholangiography, percutaneous transhepatic cholangiography, hepatocyte differentiation, HOXB2, HOXB3, regenerative medicine
- MeSH terms
- Adolescent, Adult, Aged, Bile Acids and Salts, Bile Ducts, Female, Humans, Male, Middle Aged, Organoids, Phenotype
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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