Construction of a Portal Implantable Functional Tissue-Engineered Liver Using Perfusion-Decellularized Matrix and Hepatocytes in Rats
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Innovative cell-based therapies, including hepatic tissue engineering following hepatocyte transplantation, are considered as theoretical alternatives to liver transplant or for partial replacement of liver function in patients. However, recent progress in hepatic tissue engineering has been hampered by low initial hepatocyte engraftment and insufficient blood supply in vivo. We developed an intact 3D scaffold of an extracellular matrix (ECM) derived from a decellularized liver lobe, with layer-by-layer (LbL) heparin deposition to avoid thrombosis, which we repopulated with hepatocytes and successfully implanted as a tissue-engineered liver (TEL) into the portal system. The TEL provided sufficient volume for transplantation of cell numbers representing up to 10% of whole-liver equivalents and was perfused by portal vein blood. Treatment of extended hepatectomized rats with a TEL improved liver function and prolonged survival; mean lifespan was extended from 16 to 72 h. At 72 h postoperation, the TEL sustained functional and viable hepatocytes. In conclusion, we propose the TEL as a state-of-the-art substitute for whole-liver transplantation and as a proof of concept for the technology that will eventually allow for the transplantation of a reconstituted liver.
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In a 90% hepatectomized rodent model, transplanted heparin-pretreated decellularized liver lobes recellularized with rat hepatocyte spheroids supported hepatic function for 72 h, preserved hepatocyte morphology, and prolonged animal survival.
“Transplanted grafts supported hepatic function for 72 h, preserving hepatocyte morphology and prolonging animal survival.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [218]
Bao et al. were the first to describe heparin immobilization within rat liver scaffold, primarily for reducing coagulation in vivo rather than improving reendothelialization efficiency.
“Bao et al. were the first to describe heparin immobilization within rat liver scaffold, primarily for reducing coagulation in vivo rather than improving reendothelialization efficiency [218].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [218]
In 90% hepatectomized rats, a heparin-deposited decellularized rat liver repopulated with hepatocytes and transplanted into the portal system for 72 h improved liver function, decreased blood ammonia levels, and prolonged survival compared to 90% hepatectomy.
“The transplanted scaffold improved liver function, decreased blood ammonia levels, and prolonged survival compared to a 90 % hepatectomy.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [218]
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- Authors
- Bao, J., Shi, Y., Sun, H., Yin, X., Yang, R., Li, L., Chen, X., & Bu, H.
- Affiliations
- Sichuan University (CN)
- Venue
- Cell Transplantation
- Publisher
- SAGE Publications
- Published
- 2011-06
- Volume
- 20
- Issue
- 5
- Pages
- 753-766
- ISSN
- 0963-6897 (ISSN-L)
- 1555-3892
- OpenAlex
- W1965557044
- Cited by
- 133
- References
- 29
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 12 · 2020: 6 · 2019: 13 · 2018: 9 · 2017: 15 · 2016: 14 · 2015: 14 · 2014: 12 · 2013: 12 · 2012: 5
- FWCI
- 7.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Transplantation (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
- hepatocyte transplantation, extracellular matrix scaffolds, heparin coating, thromboprophylaxis, portal vein perfusion, extended hepatectomy, liver transplantation alternatives, hepatocyte engraftment, rat model
- MeSH terms
- Animals, Extracellular Matrix, Liver Diseases, Male, Portal Vein, Rats, Inbred Lew, Liver Transplantation, Liver, Artificial, Hepatocytes, Tissue Engineering, Rats
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