Scaffolds obtained from decellularized human extrahepatic bile ducts support organoids to establish functional biliary tissue in a dish
Open accessAbstract
Biliary disorders can lead to life‐threatening disease and are also a challenging complication of liver transplantation. As there are limited treatment options, tissue engineered bile ducts could be employed to replace or repair damaged bile ducts. We explored how these constructs can be created by seeding hepatobiliary LGR5+ organoids onto tissue‐specific scaffold. For this, we decellularized discarded human extrahepatic bile ducts (EBD) that we recellularized with organoids of different origin, that is, liver biopsies, extrahepatic bile duct biopsies, and bile samples. Here, we demonstrate efficient decellularization of EBD tissue. Recellularization of the EBD extracellular matrix (ECM) with the organoids of extrahepatic origin (EBD tissue and bile derived organoids) showed more profound repopulation of the ductal ECM when compared with liver tissue (intrahepatic bile duct) derived organoids. The bile duct constructs that were repopulated with extrahepatic organoids expressed mature cholangiocyte‐markers and had increased electrical resistance, indicating restoration of the barrier function. Therefore, the organoids of extrahepatic sources are identified to be the optimal candidate for the development of personalized tissue engineered EBD constructs.
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At the end of the 21-day period, decellularized human extrahepatic bile duct scaffolds exhibited full luminal surface coverage with a confluent monolayer of cholangiocyte-like cells following reseeding.
“At the end of the 21-day period, the decellularized human extrahepatic bile duct scaffolds exhibited full luminal surface coverage with a confluent monolayer of cholangiocyte-like cells following reseeding.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [256]
The Results (Figure 3; page not available) report that, after 21 days, extrahepatic bile duct–derived and bile-derived organoids formed confluent monolayers covering the entire luminal surface of the ECM discs, with cholangiocyte-like features. The claim omits the qualification that intrahepatic bile duct–derived organoids did not consistently achieve full coverage; it also describes the tested discs as though they were whole duct scaffolds. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRepopulated cells expressed mature cholangiocyte markers including KRT 7, KRT 19, CFTR, and SCTR.
“Repopulated cells expressed different mature cholangiocyte markers including KRT 7, KRT 19, CFTR, and SCTR.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [256]
The Results (page not supplied) report KRT-7 and KRT-19 protein expression in repopulated scaffolds and detect CFTR gene expression in recellularized samples. The cited passages do not report SCTR expression, so the full list of markers is not supported. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCompared to organoids of intrahepatic origin, extrahepatic and bile-derived organoids demonstrated more efficient repopulation of the decellularized duct.
“Compared to organoids of intra hepatic origin, extra hepatic and bile-derived organoids demonstrated more efficient repopulation of the decellularized duct.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [256]
Extrahepatic and bile-derived organoids displayed profound tight junctions and polarity with apical cilia, with expression of mature cholangiocyte markers and increased electrical resistance, suggesting restoration of the barrier function.
“Additionally, extrahepatic and bile-derived organoids displayed profound tight junctions and polarity with apical cilia, with expression of mature cholangiocyte markers and increased electrical resistance, suggesting the restoration of the barrier function.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [256]
After 7-10 days of recellularization of the bile duct disc, a transparent rim was seen surrounding the edge of the decellularized duct in extrahepatic and bile-derived organoid-recellularized samples, but this rim was not clear and did not cover the entire disc in intrahepatic organoid-recellularized ducts.
“After 7–10 days of recellularization of the bile duct disc, a transparent rim was seen surrounding the edge of the decellularized duct in extrahepatic and bile-derived organoid-recellularized samples. This rim was not clear and did not cover the entire disc in the case of intra hepatic organoid-recellularized ducts.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [256]
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“Willemse et al. recellularized discarded decellularized human extrahepatic bile ducts with cholangiocyte organoids obtained from different origins including liver biopsies, extrahepatic bile duct biopsies, and bile samples [256].”
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- Authors
- Willemse, J., Roos, F. J. M., Voogt, I. J., Schurink, I. J., Bijvelds, M., de Jonge, H. R., van der Laan, L. J. W., de Jonge, J., & Verstegen, M. M. A.
- Affiliations
- Erasmus MC (NL)
- Department of Gastroenterology and Hepatology Erasmus MC‐University Medical Center Rotterdam The Netherlands
- Department of Surgery Erasmus MC‐University Medical Center Rotterdam The Netherlands
- Corresponding author
- Verstegen, Monique M. A.
- ORCID
- Venue
- Biotechnology and Bioengineering
- Publisher
- Wiley
- Published
- 2020-11-09
- Volume
- 118
- Issue
- 2
- Pages
- 836-851
- ISSN
- 0006-3592 (ISSN-L)
- 1097-0290
- PMC
- PMC7894321
- OpenAlex
- W3097610187
- Cited by
- 35
- References
- 29
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 10 · 2021: 5 · 2020: 1
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biotechnology and Bioengineering (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Cystic Fibrosis Trust (SRC011)
- Technische Universiteit Delft
- Medical Delta
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- recellularization, extracellular matrix, biliary tract diseases, liver transplantation complications
- MeSH terms
- Epithelial Cells, Extracellular Matrix, Humans, Organoids, Bile Ducts, Extrahepatic, Tissue Engineering, Tissue Scaffolds
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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