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Human-Scale Whole-Organ Bioengineering for Liver Transplantation: A Regenerative Medicine Approach
Open accessAbstract
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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“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]
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“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]
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“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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Metadata
- 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
- 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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