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

M. Dandri, M. R. Burda, E. Török, J. M. Polok, A. Iwanska, G. Sommer, X. Rogiers, C. E. Rogler, Sanjeev Gupta, H. Will, H. Greten, J. Petersen

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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

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Hepatitis B virus
Hepatocytes
Liver
Infection
Urokinase-Type Plasminogen Activator
Transcriptional Activation
Liver Diseases
Transplantation
Viruses
Virus Diseases
Cell Division
Albumins
Cell Line
DNA

ASJC Scopus subject areas

  • Hepatology

Cite this

Dandri, M., Burda, M. R., Török, E., Polok, J. M., Iwanska, A., Sommer, G., ... 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

Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus. / Dandri, M.; Burda, M. R.; Török, E.; Polok, J. M.; Iwanska, A.; Sommer, G.; Rogiers, X.; Rogler, C. E.; Gupta, Sanjeev; Will, H.; Greten, H.; Petersen, J.

In: Hepatology, Vol. 33, No. 4, 2001, p. 981-988.

Research output: Contribution to journalArticle

Dandri, M, Burda, MR, Török, E, Polok, JM, Iwanska, A, Sommer, G, Rogiers, X, Rogler, CE, 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, vol. 33, no. 4, pp. 981-988. https://doi.org/10.1053/jhep.2001.23314
Dandri, M. ; Burda, M. R. ; Török, E. ; Polok, J. M. ; Iwanska, A. ; Sommer, G. ; Rogiers, X. ; Rogler, C. E. ; Gupta, Sanjeev ; Will, H. ; Greten, H. ; Petersen, J. / Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus. In: Hepatology. 2001 ; Vol. 33, No. 4. pp. 981-988.
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