| Project/Area Number |
15590661
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nagasaki University |
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Principal Investigator |
HAMASAKI Keisuke (2004) Nagasaki University, Medical Hospital, lecturer, 医学部・歯学部附属病院, 講師 (50333521)
石川 博基 (2003) 長崎大学, 医学部・歯学部附属病院, 助手 (30346960)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAO Kazuhiko Nagasaki University, Health Research Center, associate professor, 保健管理センター, 助教授 (00264218)
浜崎 圭輔 長崎大学, 医学部・歯学部附属病院, 講師 (50333521)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Hepatocellular carcinoma / Bone marrow stem cell / 肝再生 / 骨髄細胞 / 遺伝子治療 |
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| Research Abstract |
BACKGROUND AND AIM : Recent studies indicated that hepatic stem cells in the bone marrow could differentiate into mature hepatocytes, suggesting that bone marrow cells could be used for replacement of damaged hepatocytes in a variety of liver diseases. Hepatocellular carcinoma(HCC) is thought to arise from hepatic stem cells. In this study, we investigated the malignant potential of hepatic stem cells derived from the bone marrow in a mouse model of chemical hepatocarcinogenesis. METHODS : Bone marrow cells were obtained from the male beta-galactosidase(beta-gal) transgenic mouse and transplanted into female recipient mice. Hepatocarcinogenesis was induced by a year of treatment with diethylnitrosamine and phenobarbital(NDEA/PB). One year later, the liver was removed from each treated mouse and evaluated by x-gal staining, immunohistochemistry, and fluorescence in situ hybridisation(FISH). RESULTS : Forty per cent of recipient mice survived and developed multiple HCC. Clusters of beta-gal positive mature hepatocytes were detected sporadically in the entire liver of NDEA/PB treated mice who underwent bone marrow transplantation(BMT) with while no such hepatocytes were identified in the liver of BMT mice that were not treated with NDEA/PB. The Y chromosome was detected with the same frequency as the donor male liver in clusters of beta-gal positive mature hepatocytes by FISH. However, no HCC was positive for beta-gal or the Y chromosome. Immunohistochemically, beta-gal positive mature hepatocytes did not express CD34 or alpha-fetoprotein. CONCLUSIONS : Our results suggest that hepatic stem cells derived from the bone marrow have low malignant potential, at least in our model.
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