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¹ Yoshizato Project, Cooperative Link of Unique Science and Technology for Economy Revitalization, Hiroshima Prefectural Institute of Industrial Science and Technology, 3-10-32 Kagamiyama, Higashihiroshima, Hiroshima 739-0046, Japan
² Division of Frontier Medical Science, Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
³ Hiroshima University Liver Project Research Center, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
⁴ PhoenixBio Co. Ltd, 3-4-1 Kagamiyama, Higashihiroshima, Hiroshima 739-0046, Japan
⁵ Developmental Biology Laboratory and Hiroshima University 21st Century COE Program for Advanced Radiation Casualty Medicine, Department of Biological Science, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashihiroshima, Hiroshima 739-8526, Japan

(Correspondence should be addressed to K Yoshizato; Email: katsutoshi.yoshizato{at}phoenixbio.co.jp)

(C Tateno and K Yoshizato are now at PhoenixBio Co. Ltd, 3-4-1 Kagamiyama, Higashihiroshima, Hiroshima 739-0046, Japan)
(R Utoh is now at Institute of Advanced Life and Medical Sciences, Tokyo Women’s Medical College, Kawada-chou 8-6, Shinjuku-ku, Tokyo 162-8666, Japan)

We investigated effects of human (h) GH on the proliferation of h-hepatocytes that had been engrafted in the liver of albumin enhancer/promoter driven-urokinase plasminogen activator transgenic/severe combined immunodeficiency disease (uPA/SCID) mice (chimeric mice). The h-hepatocytes therein were considered to be deficient in GH, because hGH receptor (hGHR) is unresponsive to mouse GH. Actually, hIGF-1 was undetectable in chimeric mouse sera. The uPA/SCID mice were transplanted with h-hepatocytes from a 6-year (6Y)-old donor, and were injected with recombinant hGH (rhGH). rhGH stimulated the repopulation speed of h-hepatocytes; and up-regulated hIGF-1, human signal transducers and activators of transcription (hSTAT) 3, and cell cycle regulatory genes such as human forkhead box M1, human cell division cycle 25A, and human cyclin D1. To confirm the reproducibility of these effects of rhGH, similar experiments were run using h-hepatocytes from a 46-year (46Y)-old donor. rhGH similarly enhanced their repopulation speed and up-regulated the expression of the above-tested genes, especially hIGF-1 and hSTAT1. The extent of the enhancement by rhGH was much less than that in 6Y-hepatocyte-chimeric mice most probably due to the difference in GHR expression levels between the two donors. In conclusion, this study clearly demonstrated that rhGH stimulates the proliferation of h-hepatocytes in vivo.