Volume 18, Issue 6 pp. 380-389
Original Article

Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication

Mukesh Kumar

Mukesh Kumar

Marion Bessin Liver Research Center, Cancer Research Center, Diabetes Research Center

Department of Medicine

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Sriram Bandi

Sriram Bandi

Marion Bessin Liver Research Center, Cancer Research Center, Diabetes Research Center

Department of Medicine

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Kang Cheng

Kang Cheng

Marion Bessin Liver Research Center, Cancer Research Center, Diabetes Research Center

Department of Medicine

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Sanjeev Gupta

Sanjeev Gupta

Marion Bessin Liver Research Center, Cancer Research Center, Diabetes Research Center

Department of Medicine

Department of Pathology, Institute for Clinical and Translational Research, and Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA

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First published: 15 December 2011
Citations: 3
Address reprint requests to Sanjeev Gupta, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Ullmann Bldg., Rm 625, Bronx, NY 10461, USA
(E-mail: [email protected]; [email protected])

Abstract

Kumar M, Bandi S, Cheng K, Gupta S. Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication. Xenotransplantation 2011; 18: 380–389. © 2011 John Wiley & Sons A/S.

Abstract: Background: Studies of natural hepatitis B virus infection must be restricted to humans or primates due to viral species-specificity. Alternative hepadnavirus animal models, e.g., woodchuck hepatitis virus in captive woodchucks, are not convenient, while in transgenic mice hepatitis B virus or viral proteins are expressed permanently through integrated genomes. Availability of small animal models that are easily produced and permit rapid assays will be quite helpful.

Aims: We examined whether transplantation of human cells in the peritoneal cavity of mice will generate an appropriate mass of cells with hepatitis B virus replication.

Methods: HepG2 2.2.15 cells were transplanted intraperitoneally into NOD/SCID mice. Replication of hepatitis B virus and viral gene expression was determined by analysis of blood and transplanted tissues with viral DNA and hepatitis B core antigen expression. Interruption of viral replication was examined.

Results: After intraperitoneal transplantation with microcarrier scaffolds, 2.2.15 cells engrafted and proliferated in the peritoneal cavity of NOD/SCID mice. Hepatitis B virus replicated in transplanted 2.2.15 cells as shown by hepatitis B core antigen expression. Moreover, viral particles were secreted into the blood. Hepatitis B virus replication was susceptible to conventional antiviral drug therapy, such as lamivudine, as well as experimental antiviral gene therapy with a synthetic mimic of an antiviral cellular microRNA.

Conclusions: Intraperitoneal transplantation of human cells rapidly provided reservoirs of hepatitis B virus in mice. This simple xenotransplantation approach will be effective and convenient for studies of hepatitis B and other human viruses in vivo.

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