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Hum Gene Ther. 2005 Oct;16(10):1168-74.

Efficient in vivo xenogeneic retroviral vector-mediated gene transduction into human hepatocytes.

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Yoshizato Project, Cooperative Link of Unique Science and Technology for Economy Revitalization (CLUSTER), Hiroshima Prefectural Institute of Industrial Science and Technology, Higashihiroshima, Hiroshima 739-0046, Japan.


We developed a method for efficient retroviral vector-mediated gene transfer into human hepatocytes, using a human hepatocyte-bearing mouse model. Normal human hepatocytes were transplanted into the livers of immunodeficient and liver-damaged mice. Donor hepatocytes multiplied and replaced the host hepatocytes, which yielded human hepatocyte-bearing mice (human hepatocyte-chimeric mice). As control cells, rat hepatocytes were similarly transplanted. The replacement level reached 86% at 8 weeks and 100% at 5 weeks posttransplantation of human and rat hepatocytes, respectively. Human and rat hepatocytes in the host liver showed a high bromodeoxyuridine-labeling index during the first 2 weeks posttransplantation. Human- and rat-chimeric mice were injected 7 and 10 days posttransplantation, respectively, with retroviral vectors carrying the beta-galactosidase gene and were thereafter injected daily for 20 and 10 days, respectively. The level of beta-galactosidase-positive hepatocytes in the human- and rat-chimeric mice reached 7.1 +/- 1.8% at 8 weeks and 5.3 +/- 0.9% at 5 weeks after transplantation, respectively. The human hepatocyte-chimeric mouse will be useful for testing the ability of vectors to transduce human cells.

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