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Treatment of acetaminophen-induced acute liver failure in the mouse with conditionally immortalized human hepatocytes
Abstract
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…
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“In addition there are data suggesting that acetaminophen activates telomerase [146,147,148,149], which could lead to the immortalization of cells.”
From Cell Immortality: In Vitro Effective Techniques to Achieve and Investigate Its Applications and Challenges (2024) · cites this paper as [148]
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Cited by
Practical Use of Immortalized Cells in Medicine: Current Advances and Future Perspectives
Voloshin, N., Tyurin-Kuzmin, P., Karagyaur, M., Akopyan, Z., & Kulebyakin, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241612716 · Cited by 77
Chalak, M., Hesaraki, M., Mirbahari, S. N., Yeganeh, M., Abdi, S., Rajabi, S., & Hemmatzadeh, F. (2024) · Life · doi:10.3390/life14030417 · Cited by 66
Metadata
- Authors
- Nguyen, T. H., Mai, G., Villiger, P., Oberholzer, J., Salmon, P., Morel, P., Bühler, L., & Trono, D.
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 43
- Issue
- 6
- Pages
- 1031-1037
- ISSN
- 0168-8278
- Cited by
- 53
- References
- 2
- Language
- en
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