Human-Scale Whole-Organ Bioengineering for Liver Transplantation: A Regenerative Medicine Approach
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At this time, the only definitive treatment of hepatic failure is liver transplantation. However, transplantation has been limited by the severely limited supply of human donor livers. Alternatively, a regenerative medicine approach has been recently proposed in rodents that describe the production of three-dimensional whole-organ scaffolds for assembly of engineered complete organs. In the present study, we describe the decellularization of porcine livers to generate liver constructs at a scale that can be clinically relevant. Adult ischemic porcine livers were successfully decellularized using a customized perfusion protocol, the decellularization process preserved the ultrastructural extracellular matrix components, functional characteristics of the native microvascular and the bile drainage network of the liver, and growth factors necessary for angiogenesis and liver regeneration. Furthermore, isolated hepatocytes engrafted and reorganized in the porcine decellularized livers using a human-sized organ culture system. These results provide proof-of-principle for the generation of a human-sized, three-dimensional organ scaffold as a potential structure for human liver grafts reconstruction for transplantation to treat liver disease.
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Albumin immunostaining was lower after 7 days of media perfusion compared to day 4, attributed to shear stress caused by media flow.
“Furthermore, they observed that albumin immunostaining was lower after 7 days of media perfusion compared to day 4, attributed to shear stress caused by media flow.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [198]
The Results (Recellularization; page not provided) report that albumin immunostaining decreased considerably after seven days of perfusion culture compared with day four. The Discussion proposes optimizing perfusion flow to decrease shear stress in future studies, but does not establish shear stress as the cause of the staining decrease. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe biliary network tree is confirmed to be intact after decellularization by scan electron microscopy, corrosion cast, dye perfusion, and contrast radiography; only reconstruction by bile duct cells is necessary.
“Fortunately, the biliary network tree is confirmed to be intact after decellularization by scan electron microscopy, corrosion cast, dye perfusion, and contrast radiography; only reconstruction by bile duct cells is necessary [12,110,170,198].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [198]
The Results section (Vascular and Bile Duct Morphology; page unavailable) reports that bile ducts were mostly intact after decellularization, but notes disruption of smaller branches and contrast retention at the biliary tree’s periphery. The Discussion says biliary epithelial cells would be needed for bile drainage, but does not establish that adding those cells is the only reconstruction needed. The paper also does not show that each of the four listed techniques confirmed an intact biliary tree. (LLM, conf=0.88)
Experimental — accuracy not yet measuredYagi et al. reported that around 47.8% of reseeded hepatocytes were apoptotic by day 7 in decellularized porcine livers.
“Importantly, they reported that around 47.8 % of reseeded hepatocytes were apoptotic by day 7.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [198]
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- Authors
- Yagi, H., Fukumitsu, K., Fukuda, K., Kitago, M., Shinoda, M., Obara, H., Itano, O., Kawachi, S., Tanabe, M., Coudriet, G. M., Piganelli, J. D., Gilbert, T. W., Soto-Gutierrez, A., & Kitagawa, Y.
- Affiliations
- Keio University (JP)
- University of Pittsburgh (US)
- Department of Pathology, Center for Innovative Regenerative Therapies, Department of Surgery, Transplantation Section, Children's Hospital of Pittsburgh and the Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
- Corresponding author
- Kitagawa, Yuko
- ORCID
- Venue
- Cell Transplantation
- Publisher
- SAGE Publications
- Published
- 2013-02
- Volume
- 22
- Issue
- 2
- Pages
- 231-242
- ISSN
- 0963-6897 (ISSN-L)
- 1555-3892
- PMC
- PMC3682787
- OpenAlex
- W2073329698
- Cited by
- 188
- References
- 34
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 5 · 2023: 8 · 2022: 16 · 2021: 14 · 2020: 9 · 2019: 17 · 2018: 15 · 2017: 20 · 2016: 25 · 2015: 24 · 2014: 13 · 2013: 8 · 2012: 2
- FWCI
- 15.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cell Transplantation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Astellas Pharma
- Japan Society for the Promotion of Science (23689059)
- National Institute of Diabetes and Digestive and Kidney Diseases (K99DK083556, DK083556, R00DK083556)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- liver transplantation, decellularization, porcine liver, extracellular matrix, perfusion protocols, hepatocyte engraftment, organ culture, liver regeneration, angiogenesis, organ shortage, regenerative medicine
- MeSH terms
- Animals, Cells, Cultured, Liver, Male, Swine, Liver Transplantation, Hepatocytes, Tissue Engineering, Regenerative Medicine
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