Generation and metabolomic characterization of functional ductal organoids with biliary tree networks in decellularized liver scaffolds
Open accessAbstract
Developing functional ductal organoids (FDOs) is essential for liver regenerative medicine. We aimed to construct FDOs with biliary tree networks in rat decellularized liver scaffolds (DLSs) with primary cholangiocytes isolated from mouse bile ducts. The developed FDOs were dynamically characterized by functional assays and metabolomics for bioprocess clarification. FDOs were reconstructed in DLSs retaining native structure and bioactive factors with mouse primary cholangiocytes expressing enriched biomarkers. Morphological assessment showed that biliary tree-like structures gradually formed from day 3 to day 14. The cholangiocytes in FDOs maintained high viability and expressed 11 specific biomarkers. Basal-apical polarity was observed at day 14 with immunostaining for E-cadherin and acetylated α-tubulin. The rhodamine 123 transport assay and active collection of cholyl-lysyl-fluorescein exhibited the specific functions of bile secretion and transportation at day 14 compared to those in monolayer and hydrogel culture systems. The metabolomics analysis with 1075 peak pairs showed that serotonin, as a key molecule of the tryptophan metabolism pathway linked to biliary tree reconstruction, was specifically expressed in FDOs during the whole period of culture. Such FDOs with biliary tree networks and serotonin expression may be applied for disease modeling and drug screening, which paves the way for future clinical therapeutic applications.
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Chen et al. successfully developed functional ductal organoids (FDOs) within decellularized rat liver scaffolds, demonstrating the formation of biliary tree-like structures, maintenance of high viability and expression of specific biomarkers by primary cholangiocytes, and highlighting serotonin's key role in biliary tree reconstruction.
“Chen et al. successfully developed functional ductal organoids (FDOs) within decellularized rat liver scaffolds, demonstrating the formation of biliary tree-like structures, maintenance of high viability and expression of specific biomarkers by primary cholangiocytes, and highlighting serotonin's key role in biliary tree reconstruction [46].”
From Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models (2025) · cites this paper as [46]
Transplant waiting lists are growing faster than donor availability, and long-term outcomes are complicated by rejection and immunosuppression.
“Yet, with transplant waiting lists growing faster than donor availability, and long-term outcomes still complicated by rejection and immunosuppression, it's clear we need better alternatives [[3], [4], [5]].”
Liver transplantation remains the only definitive cure for end-stage liver disease.
“For patients with end-stage disease, liver transplantation remains the only definitive cure.”
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“…organoids (FDOs) within decellularized rat liver scaffolds, demonstrating the formation of biliary tree-like structures, maintenance of high viability and expression of specific biomarkers by primary chol-angiocytes, and highlighting serotonin ’ s key role in biliary tree reconstruction [46].”
BackgroundMajidi, Z., Sarvi, M. M., Rajabi, M. A., Firouzian, H., Seyhoun, I., & Majidi Zolbin, M. (2026) · Regenerative Therapy · doi:10.1016/j.reth.2025.11.006 · Cited by 5 · see citing works
- Authors
- Chen, J., Ma, S., Yang, H., Liang, X., Yao, H., Guo, B., Chen, D., Jiang, J., Shi, D., Xin, J., Ren, K., Zhou, X., Li, Y., Geng, L., & Li, J.
- Affiliations
- First Affiliated Hospital Zhejiang University (CN)
- Taizhou Central Hospital (CN)
- Zhejiang University (CN)
- Corresponding author
- Geng, Lei
- ORCID
- Venue
- Bioactive Materials
- Publisher
- Elsevier BV
- Published
- 2023-08
- Volume
- 26
- Pages
- 452-464
- ISSN
- 2097-1192 (ISSN-L)
- 2452-199X
- PMC
- PMC10073412
- OpenAlex
- W4361215910
- Cited by
- 20
- References
- 6
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 3
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Bioactive Materials (publishedVersion, cc-by-nc-nd)
- SSRN Electronic Journal (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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
- decellularized liver scaffold, cholangiocytes, bile secretion, bile transport, serotonin, tryptophan metabolism, liver regeneration, metabolomics, disease modeling
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