Therapeutic Liver Reconstitution With Murine Cells Isolated Long After Death
Open accessAbstract
Background & aims Due to the shortage of donor organs, many patients needing liver transplantation cannot receive one. For some liver diseases, hepatocyte transplantation could be a viable alternative, but donor cells currently are procured from the same sources as whole organs, and thus the supply is severely limited.Methods Here, we investigated the possibility of isolating viable hepatocytes for liver cell therapy from the plentiful source of morgue cadavers. To determine the utility of this approach, cells were isolated from the livers of non-heart-beating cadaveric mice long after death and transplanted into fumarylacetoacetate hydrolase-deficient mice, a model for the human metabolic liver disease hereditary tyrosinemia type I and a stringent in vivo model for hepatic cell transplantation.Results Surprisingly, complete and therapeutic liver repopulation could be achieved with hepatocytes derived up to 27 hours post mortem.Conclusions Competitive repopulation experiments showed that cadaveric liver cells had a repopulation capacity similar to freshly isolated hepatocytes. Importantly, viable hepatocytes also could be isolated from cadaveric primate liver (monkey and human) efficiently. These data provide evidence that non-heart-beating donors could be a suitable source of hepatocytes for much longer time periods than previously thought possible.
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Hepatocytes have a high replicative potential in vivo.
“Hepatocytes have a high replicative potential in vivo3, 4, however hepatocyte isolation is technically demanding, requires cadaveric liver donation, and hepatocytes cannot be expanded effectively in vitro5.”
From Hepatic progenitor cells of biliary origin with liver repopulation capacity (2015) · cites this paper as [4]
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- Authors
- Erker, L., Azuma, H., Lee, A. Y., Guo, C., Orloff, S., Eaton, L., Benedetti, E., Jensen, B., Finegold, M., Willenbring, H., & Grompe, M.
- Affiliations
- Oregon Health & Science University (US)
- University of California, San Francisco (US)
- Texas Children's Hospital (US)
- Corresponding author
- Erker, Laura
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 139
- Issue
- 3
- Pages
- 1019-1029
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC3786690
- OpenAlex
- W2148914475
- Cited by
- 34
- References
- 26
- Citations by year
- 2024: 2 · 2023: 1 · 2021: 5 · 2020: 1 · 2019: 1 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 6 · 2012: 4
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK56338, R01DK051592, P30DK056338)
- National Center for Research Resources (P51RR000163, K01RR000163, RR-00163.)
- Topics
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- hepatocyte transplantation, liver cell therapy, donation after circulatory death, tyrosinemia type I, fumarylacetoacetate hydrolase deficiency, liver repopulation
- MeSH terms
- Animals, Cadaver, Cell Separation, Cell Survival, Cells, Cultured, Disease Models, Animal, Humans, Hydrolases, Liver, Liver Regeneration, Macaca mulatta, Proteins, Temperature, Time Factors, Tyrosine, Biomarkers, Mice, Knockout, Tyrosinemias, RNA, Untranslated, Hepatocytes, Cell Proliferation, Mice
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