| Treatment of acetaminophen-induced acute liver failure in the mouse with conditionally immortalized human hepatocytes. | |
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MedLine Citation:
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PMID: 16169114 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Liver failure is a life threatening condition currently treated by palliative measures and, when applicable, organ transplantation. The use of a bioartificial organ capable of fulfilling the main functions of the liver would represent an attractive alternative. However, the shortage of suitable donor cells, and their limited growth ability have impeded the development of this strategy. We investigated whether lentiviral vectors allow for conditional immortalization of human hepatocytes and whether these immortalized hepatocytes could reverse lethal acute liver failure. METHODS: We exposed primary human hepatocytes to Cre-excisable lentiviral vectors coding for SV40T Antigen, telomerase, and/or Bmi-1 and tested the functionality of the resulting cell lines. Therapeutic potential of immortalized hepatocytes were tested in a murine model of acetaminophen-induced hepatic injury. RESULTS: The immortalized hepatocytes grew continuously yet were non-tumorigenic, stopped proliferating when exposed to Cre recombinase, and conserved defining properties of primary hepatocytes, including the ability to secrete liver-specific proteins and to detoxify drugs. The implantation of encapsulated immortalized human hepatocytes rescued mice from lethal doses of acetaminophen. CONCLUSIONS: Lentiviral vectors represent tools of choice for immortalization of non-dividing primary cells, and lentivirally immortalized human hepatocytes are promising reagents for cell-based therapy of acute liver failure. |
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Authors:
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Tuan Huy Nguyen; Gang Mai; Peter Villiger; José Oberholzer; Patrick Salmon; Philippe Morel; Leo Bühler; Didier Trono |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-07-05 |
Journal Detail:
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Title: Journal of hepatology Volume: 43 ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 2005 Dec |
Date Detail:
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Created Date: 2005-11-21 Completed Date: 2006-03-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: England |
Other Details:
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Languages: eng Pagination: 1031-7 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetaminophen
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adverse effects* Adult Analgesics, Non-Narcotic / adverse effects* Animals Cell Line, Transformed Cell Transplantation / methods* Disease Models, Animal Genetic Vectors Hepatocytes / transplantation Humans Lentivirus Liver Failure, Acute / chemically induced, therapy* Liver, Artificial* Mice |
| Chemical | |
Reg. No./Substance:
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0/Analgesics, Non-Narcotic; 103-90-2/Acetaminophen |
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