Cholangiocyte organoids can repair bile ducts after transplantation in the human liver
Open accessAbstract
Organoids regenerate human bile ducts: Bile ducts carry bile from the liver and gall bladder to the small intestine, where it aids digestion. Cholangiocytes are epithelial cells that line bile ducts and modify bile as its transported through the biliary tree. Chronic liver diseases involving cholangiocytes account for a large fraction of liver failure and the need for liver transplantation. Because liver donors are in short supply, Sampaziotis et al. used organoid technology to develop a cell-based therapy using human tissue (see the Perspective by Kurial and Willenbring). Cholangiocyte organoids were transplanted into the intrahepatic ducts of deceased human donor livers undergoing ex vivo normothermic perfusion. The livers could be maintained for up to 100 hours, and the transplanted organoids engrafted, exhibited function, and could repair bile ducts. Science , this issue p. 839 ; see also p. 786
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Undefined ECMs such as Matrigel suffer from unknown composition and batch-to-batch variability, making reproducibility a significant concern.
“Similarly, undefined ECMs (e.g. Matrigel) suffer from their unknown composition and batch to batch variability, making reproducibility a significant concern13,205.”
From Organoids (2022) · cites this paper as [205]
The organoid derivation and culture passage (Analysis of normalized 10X data; page unavailable) says the cells were cultured under the same conditions, but does not address the composition or variability of the matrix. Searches for Matrigel, batch-to-batch variability, and ECM reproducibility found no passage in our copy supporting the attributed concern. (LLM, conf=0.73)
Experimental — accuracy not yet measuredThere are two main paths to overcome the use of non-specific ECM such as Matrigel: synthetic matrices with more complete control over composition and stiffness, and decellularized tissue to create tissue-specific matrices.
“There are two main paths to overcome the use of non-specific ECM such as Matrigel: one is the use of synthetic matrices with more complete control over composition and stiffness, and the other is to take decellularized tissue and create tissue-specific matrices205,243.”
From Organoids (2022) · cites this paper as [205]
The Main text discusses how environmental cues affect cholangiocyte organoids, while the ‘Organoid derivation and culture’ passage says they were grown using an established method. Neither passage addresses two alternatives to Matrigel. Searches for synthetic matrices, stiffness, Matrigel, and decellularized tissue found no passage supporting the attributed claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredGallbladder-derived cholangiocyte organoids have been shown to engraft in the intrahepatic biliary tree after injection into deceased transplant donor livers and prevent ischemic injury while the organ is under machine perfusion.
“For example, gallbladder-derived cholangiocyte organoids have been shown to engraft in the intrahepatic biliary tree after injection into deceased transplant donor livers and prevent ischemic injury while the organ is under machine perfusion, which represents a promising example of ex vivo cell-based therapy [164].”
From Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells (2025) · cites this paper as [164]
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- Authors
- Sampaziotis, F., Muraro, D., Tysoe, O. C., Sawiak, S., Beach, T. E., Godfrey, E. M., Upponi, S. S., Brevini, T., Wesley, B. T., Garcia-Bernardo, J., Mahbubani, K., Canu, G., Gieseck, R., Berntsen, N. L., Mulcahy, V. L., Crick, K., Fear, C., Robinson, S., Swift, L., Gambardella, L., Bargehr, J., Ortmann, D., Brown, S. E., Osnato, A., Murphy, M. P., Corbett, G., Gelson, W. T. H., Mells, G. F., Humphreys, P., Davies, S. E., Amin, I., Gibbs, P., Sinha, S., Teichmann, S. A., Butler, A. J., See, T. C., Melum, E., Watson, C. J. E., Saeb-Parsy, K., & Vallier, L.
- Affiliations
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK.
- National Institutes of Health (US)
- Oslo University Hospital (NO)
- NHS Blood and Transplant (GB)
- Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, Cambridgeshire, UK.
- Corresponding author
- Sampaziotis, Fotios
- Vallier, Ludovic
- ORCID
- Sampaziotis, Fotios
- Muraro, Daniele
- Tysoe, Olivia C.
- Sawiak, Stephen
- Godfrey, Edmund M.
- Upponi, Sara S.
- Brevini, Teresa
- Wesley, Brandon T.
- Garcia-Bernardo, Jose
- Mahbubani, Krishnaa
- Canu, Giovanni
- Gieseck, Richard
- Berntsen, Natalie L.
- Mulcahy, Victoria L.
- Crick, Keziah
- Fear, Corrina
- Robinson, Sharayne
- Swift, Lisa
- Gambardella, Laure
- Bargehr, Johannes
- Brown, Stephanie E.
- Osnato, Anna
- Murphy, Michael P.
- Corbett, Gareth
- Gelson, William T. H.
- Mells, George F.
- Davies, Susan E.
- Gibbs, Paul
- Sinha, Sanjay
- Teichmann, Sarah A.
- Butler, Andrew J.
- See, Teik Choon
- Melum, Espen
- Watson, Christopher J. E.
- Saeb-Parsy, Kourosh
- Vallier, Ludovic
- Venue
- Science
- Published
- 2021-02-19
- Volume
- 371
- Issue
- 6531
- Pages
- 839-846
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7610478
- OpenAlex
- W3129440616
- Cited by
- 394
- References
- 7
- Citations by year
- 2026: 63 · 2025: 79 · 2024: 87 · 2023: 56 · 2022: 67 · 2021: 42
- FWCI
- 34.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Apollo
- Funders
- Medical Research Council
- National Institute for Health Research
- British Heart Foundation
- Academy of Medical Sciences
- European Research Council
- Rosetrees Trust
- Addenbrooke's Charitable Trust, Cambridge University Hospitals
- European Association for the Study of the Liver
- Wellcome Trust Centre for Mitochondrial Research
- Cambridge University Hospitals National Institute for Health Research Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- cholangiocyte organoids, cholangiopathy, liver transplantation, cholangiocytes, transcriptional diversity, single-cell RNA sequencing, ex vivo normothermic perfusion, cell engraftment, regenerative medicine
- MeSH terms
- RNA-Seq, Animals, Bile, Bile Duct Diseases, Bile Ducts, Bile Ducts, Intrahepatic, Common Bile Duct, Epithelial Cells, Gallbladder, Gene Expression Regulation, Humans, Liver, Tissue and Organ Procurement, Organoids, Liver Transplantation, Mesenchymal Stem Cell Transplantation, Mice, Transcriptome, Cell- and Tissue-Based Therapy
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