Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus

Maura Dandri, Martin R. Burda, Eva Török, Joerg M. Polok, Alicja Iwanska, Gunhild Sommer, Xavier Rogiers, Charles E. Rogler, Sanjeev Gupta, Hans Will, Heiner Greten, Joerg Petersen

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285 Scopus citations

Abstract

Mice containing livers repopulated with human hepatocytes would provide excellent in vivo models for studies on human liver diseases and hepatotropic viruses, for which no permissive cell lines exist. Here, we report partial repopulation of the liver of immunodeficient urokinase-type plasminogen activator (uPA)/recombinant activation gene-2 (RAG-2) mice with normal human hepatocytes isolated from the adult liver. In the transplanted mice, the production of human albumin was demonstrated, indicating that human hepatocytes remained functional in the mouse liver for at least 2 months after transplantation. Inoculation of transplanted mice with human hepatitis B virus (HBV) led to the establishment of productive HBV infection. According to human-specific genomic DNA analysis and immunostaining of cryostat liver sections, human hepatocytes were estimated to constitute up to 15% of the uPA/RAG-2 mouse liver. This is proof that normal human hepatocytes can integrate into the mouse hepatic parenchyma, undergo multiple cell divisions, and remain permissive for a human hepatotropic virus in a xenogenic liver. This system will provide new opportunities for studies on etiology and therapy of viral and nonviral human liver diseases, as well as on hepatocyte biology and hepatocellular transplantation.

Original languageEnglish (US)
Pages (from-to)981-988
Number of pages8
JournalHepatology
Volume33
Issue number4
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Hepatology

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    Dandri, M., Burda, M. R., Török, E., Polok, J. M., Iwanska, A., Sommer, G., Rogiers, X., Rogler, C. E., Gupta, S., Will, H., Greten, H., & Petersen, J. (2001). Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus. Hepatology, 33(4), 981-988. https://doi.org/10.1053/jhep.2001.23314