| Project/Area Number |
16590597
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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 | Yamaguchi University |
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Principal Investigator |
SAKAIDA Isao Yamaguchi University, Faculty of Medicine, Professor, 医学部, 教授 (80263763)
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| Co-Investigator(Kenkyū-buntansha) |
OKITA Kiwamu Yamaguchi University, Faculty of Medicine, Professor, 医学部, 教授(特命) (70107738)
TERAI Shuji Yamaguchi University, Faculty of Medicine, Research Associate, 医学部, 助手 (00332809)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | bone marrow cell / stem cell / extracellular matrix / preneoplastic lesion / cancer / 肝線維化 / 前癌性病変 / GFP / CC14 model / MMP-9 / MMP-14 |
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| Research Abstract |
We investigated the effect of bone marrow cell (BMC) transplantation on established liver fibrosis. BMCs of green fluorescent protein (GFP) mice were transplanted into 4-week carbon tetrachloride (CCl_4)-treated C57BL6 mice through the tail vein, and the mice were treated for 4 more weeks with CCl_4 (total, 8 weeks). Sirius red and GFP staining clearly indicated migrated BMCs existing along with fibers, with strong expression of matrix metalloproteinase (MMP)-9 shown by anti-MMP-9 antibodies and in situ hybridization. Double fluorescent immunohistochemistry showed the expression of MMP-9 on the GFP-positive cell surface. Film in situ zymographic analysis revealed strong gelatinolytic activity in the periportal area coinciding with the location of MMP-9-positive BMCs. Four weeks after BMC transplantation, mice had significantly reduced liver fibrosis, as assessed by hydroxyproline content of the livers, compared to that of mice treated with CCl_4 alone. Subpopulation of Liv8-negative BMCs was responsible for this fibrolytic effect. In conclusion, mice with BMC transplants with continuous CCl_4 injection had reduced liver fibrosis and a significantly improved survival rate after BMC transplantation compared with mice treated with CCl_4 alone. This finding introduces a new concept for the therapy of liver fibrosis. Also it has been known that prevention of fibrosis may reduce the carcinogenesis. Thus these results may suggest that fibrolysis bone marrow cell transplantation leads prevention of hepato-carcinogenesis.
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