Immunogenicity of Decellularized Porcine Liver for Bioengineered Hepatic Tissue
Open accessAbstract
Liver disease affects millions of patients each year. The field of regenerative medicine promises alternative therapeutic approaches, including the potential to bioengineer replacement hepatic tissue. One approach combines cells with acellular scaffolds derived from animal tissue. The goal of this study was to scale up our rodent liver decellularization method to livers of a clinically relevant size. Porcine livers were cannulated via the hepatic artery, then perfused with PBS, followed by successive Triton X-100 and SDS solutions in saline buffer. After several days of rinsing, decellularized liver samples were histologically analyzed. In addition, biopsy specimens of decellularized scaffolds were seeded with hepatoblastoma cells for cytotoxicity testing or implanted s.c. into rodents to investigate scaffold immunogenicity. Histological staining confirmed cellular clearance from pig livers, with removal of nuclei and cytoskeletal components and widespread preservation of structural extracellular molecules. Scanning electron microscopy confirmed preservation of an intact liver capsule, a porous acellular lattice structure with intact vessels and striated basement membrane. Liver scaffolds supported cells over 21 days, and no increased immune response was seen with either allogeneic (rat-into-rat) or xenogeneic (pig-into-rat) transplants over 28 days, compared with sham-operated on controls. These studies demonstrate that successful decellularization of the porcine liver could be achieved with protocols developed for rat livers, yielding nonimmunogenic scaffolds for future hepatic bioengineering studies.
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Mirmalek-Sani et al. found minimal apoptotic response of HepG2 cells to liver scaffolds after γ irradiation, confirming the noncytotoxic effect of the scaffold.
“TUNEL assay indicated minimal apoptotic response of HepG2 cells to liver scaffolds, confirming the noncytotoxic effect of the scaffold [183].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [183]
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Self-citation
- Authors
- Mirmalek-Sani, S.-H., Sullivan, D. C., Zimmerman, C., Shupe, T. D., & Petersen, B. E.
- Affiliations
- Wake Forest University Health Sciences (US)
- University of Florida (US)
- Corresponding author
- Petersen, Bryon E.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 183
- Issue
- 2
- Pages
- 558-565
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC3730770
- OpenAlex
- W2034885041
- Cited by
- 115
- References
- 53
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 16 · 2020: 10 · 2019: 16 · 2018: 4 · 2017: 11 · 2016: 11 · 2015: 16 · 2014: 5 · 2013: 1 · 2012: 1
- FWCI
- 10.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01 DK058614, R01 DK065096)
- 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
- porcine liver, acellular scaffolds, immunogenicity, liver regeneration, xenotransplantation, allograft, hepatoblastoma cells, Triton X-100, sodium dodecyl sulfate, extracellular matrix preservation
- MeSH terms
- Animals, Liver, Male, Rats, Inbred F344, Swine, Transplantation, Heterologous, Liver Transplantation, Tissue Engineering, Sus scrofa, Regenerative Medicine, Rats, Tissue Scaffolds
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