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The reconstituted ‘humanized liver’ in TK-NOG mice is mature and functional
Open accessAbstract
To overcome the limitations of existing models, we developed a novel experimental in vivo platform for replacing mouse liver with functioning human liver tissue. To do this, a herpes simplex virus type 1 thymidine kinase (HSVtk) transgene was expressed within the liver of highly immunodeficient NOG mice (TK-NOG). Mouse liver cells gancyclovir (GCV), and transplanted human liver cells are stably maintained within the liver (humanized TK-NOG) without exogenous drug. The reconstituted liver was shown to be a mature and functioning “human organ” that had zonal position-specific enzyme expression and a global gene expression pattern representative of mature human liver; and could generate a human-specific profile of drug metabolism. The ‘humanized liver’ could be stably maintained in these mice with a high level of synthetic function for a prolonged period (8 months). This novel in vivo system provides an optimized platform for studying human liver physiology, including drug metabolism, toxicology, or liver regeneration.
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Igarashi, R., Oda, M., Okada, R., Yano, T., Takahashi, S., Pastuhov, S., Matano, M., Masuda, N., Togasaki, K., Ohta, Y., et al. (2025) · Nature · doi:10.1038/s41586-025-08861-y · Cited by 85
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Metadata
- Authors
- Hasegawa, M., Kawai, K., Mitsui, T., Taniguchi, K., Monnai, M., Wakui, M., Ito, M., Suematsu, M., Peltz, G., Nakamura, M., & Suemizu, H.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 405
- Issue
- 3
- Pages
- 405-410
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1977229182
- Cited by
- 316
- References
- 0
- FWCI
- 9.17
- Type
- journal article
- Language
- en
- Open access
- green
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- Hasegawa, M., Kawai, K., Mitsui, T., Taniguchi, K., Monnai, M., Wakui, M., Ito, M., Suematsu, M., Peltz, G., Nakamura, M., & Suemizu, H. (2011). The reconstituted ‘humanized liver’ in TK-NOG mice is mature and functional. Biochemical and Biophysical Research Communications. https://doi.org/10.1016/j.bbrc.2011.01.042
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