Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes
Abstract
Because of a critical shortage in suitable organs, many patients with terminal liver disease die each year before liver transplantation can be performed. Transplantation of isolated hepatocytes has been proposed for the temporary metabolic support of patients awaiting liver transplantation or spontaneous reversion of their liver disease. A major limitation of this form of therapy is the present inability to isolate an adequate number of transplantable hepatocytes. A highly differentiated cell line, NKNT-3, was generated by retroviral transfer in normal primary adult human hepatocytes of an immortalizing gene that can be subsequently and completely excised by Cre/Lox site-specific recombination. When transplanted into the spleen of rats under transient immunosuppression, reversibly immortalized NKNT-3 cells provided life-saving metabolic support during acute liver failure induced by 90% hepatectomy.
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No in vivo repopulation was demonstrated using cells obtained by immortalization with hTERT and viral genes.
“However, no in vivo repopulation was demonstrated using cells thus obtained”
From In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity (2018) · cites this paper as Kobayashi et al., 2000
Efforts have been made to expand HHs by immortalization with hTERT and viral genes such as SV40, E6, and E7.
“In other studies, effort was made to expand HHs by immortalization with hTERT and viral genes, such as SV40, E6, and E7 (Kobayashi et al., 2000; Levy et al., 2015”
From In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity (2018) · cites this paper as Kobayashi et al., 2000
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Cell and tissue engineering for liver disease
Bhatia, S. N., Underhill, G. H., Zaret, K. S., & Fox, I. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3005975 · Cited by 309 · see citing works
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In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity
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- Authors
- Kobayashi, N., Fujiwara, T., Westerman, K. A., Inoue, Y., Sakaguchi, M., Noguchi, H., Miyazaki, M., Cai, J., Tanaka, N., Fox, I. J., & Leboulch, P.
- Affiliations
- Okayama University (JP)
- First Department of Surgery and
- Massachusetts Institute of Technology (US)
- University of Nebraska Medical Center (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Kobayashi, Naoya
- Fox, Ira J.
- Leboulch, Philippe
- ORCID
- Venue
- Science
- Published
- 2000-02-18
- Volume
- 287
- Issue
- 5456
- Pages
- 1258-1262
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2129501023
- Cited by
- 331
- References
- 1
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 8 · 2017: 5 · 2016: 2 · 2015: 6 · 2014: 9 · 2013: 6 · 2012: 18
- FWCI
- 29.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL55435, P01HL055435)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK48794, R01DK048794)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- acute liver failure, hepatocyte transplantation, retroviral gene transfer, hepatectomy, metabolic support, liver transplantation, immunosuppression, end-stage liver disease
- MeSH terms
- Adult, Animals, Antigens, Polyomavirus Transforming, Cell Differentiation, Cell Line, Genetic Vectors, Hepatectomy, Humans, Liver, Liver Regeneration, Retroviridae, Spleen, Transfection, Viral Proteins, Gene Expression, Mice, SCID, Liver Failure, Acute, Cell Transplantation, Cell Culture Techniques, Integrases, Mice, Rats
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