Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver grafts
Published version of a preprint
Abstract
Three-dimensional scaffolds decellularized from native organs are a promising technique to establish engineered liver grafts and overcome the current shortage of donor organs. However, limited sources of bile duct cells and inappropriate cell distribution in bioengineered liver grafts have hindered their practical application. Organoid technology is anticipated to be an excellent tool for the advancement of regenerative medicine. In the present study, we reconstructed intrahepatic bile ducts in a rat decellularized liver graft by recellularization with liver ductal organoids. Using an ex vivo perfusion culture system, we demonstrated the biliary characteristics of repopulated mouse liver organoids, which maintained bile duct markers and reconstructed biliary tree-like networks with luminal structures. We also established a method for the co-recellularization with engineered bile ducts and primary hepatocytes, revealing the appropriate cell distribution to mimic the native liver. We then utilized this model in human organoids to demonstrate the reconstructed bile ducts. Our results show that liver ductal organoids are a potential cell source for bile ducts from bioengineered liver grafts using three-dimensional scaffolds.
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Upon ex vivo culture perfusion for 3-5 days, repopulated liver ductal organoids engrafted along bile duct walls, reconstructed biliary tree-like networks with luminal structures, and expressed cholangiocyte marker genes (KRT 19, Sox 9, CFTR, Hnf1b) and sustained stemness markers (Lgr5, Prom 1).
“Upon ex vivo culture perfusion for 3–5 days, the repopulated organoids engrafted along the bile duct walls, reconstructed biliary tree-like networks with luminal structures, and expressed cholangiocyte marker genes (Fig. 5), including KRT 19, Sox 9, CFTR, and Hnf1b, and sustained the expression of stemness markers (Lgr5, Prom 1).”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [255]
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Strategies for decellularization, re-cellularization and crosslinking in liver bioengineering
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- Authors
- Tomofuji, K., Fukumitsu, K., Kondo, J., Horie, H., Makino, K., Wakama, S., Ito, T., Oshima, Y., Ogiso, S., Ishii, T., Inoue, M., & Hatano, E.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Fukumitsu, Ken
- Kondo, Jumpei
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 287
- Pages
- 121614
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W4281832623
- Cited by
- 24
- References
- 8
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 1
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22K08689, 21H02714)
- 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, 3D scaffolds, hepatocytes, biliary tract
- MeSH terms
- Animals, Bile Ducts, Bile Ducts, Intrahepatic, Biliary Tract, Humans, Liver, Organoids, Tissue Engineering, Mice, Rats, Tissue Scaffolds
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