| Project/Area Number |
16K09354
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nagoya University |
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Principal Investigator |
Ishikawa Tetsuya 名古屋大学, 医学系研究科(保健), 教授 (10288508)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 弘康 岐阜大学, 大学院医学系研究科, 准教授 (80373075)
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| Research Collaborator |
YUKAWA Hiroshi
MATSUNAGA Tamihide
SUEMIZU Hiroshi
HAYASHI Yumi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 肝細胞キメラマウス / 細胞移植 / 免疫拒絶 / 肝不全 / 肝細胞移植 / 肝細胞置換率 / GFP / 戻し交配 / 量子ドット / 再生医療 / イメージング / GVHD |
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| Outline of Final Research Achievements |
Hepatocyte-chimera mouse system was established as a model for the cell transplantation treatment with hepatocytes or stem cell-derived cells. In the transgenic mice, HSVtk that express the thymidine kinase of human herpes simplex virus in their hepatocytes, administration of ganciclovir (GCV) kills autologous hepatocytes, enabling transplantation of hepatocytes of other origin. In the case of allogenic hepatocyte transplantation into HSVtk, all the transplanted cells were eliminated by a strong immune-rejection response. In the case of syngeneic hepatocytes expressing foreign antigens, efficient engraftment of transplanted cells was observed, while inflammatory cells infiltration around the engrafted cells and cellular immune response to the foreign antigens were confirmed. The hepatocyte-chimeric mouse system can be a useful model for elucidating the mechanism of immune rejection in the cell transplantation in the liver and for studying a therapeutic method for immune rejection.
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| Academic Significance and Societal Importance of the Research Achievements |
重症な急性・慢性肝不全に対する治療として、生体肝移植、脳死肝移植が実施されているものの、ドナーの絶対的な不足により、適応症例に対しても治療の提供が困難な状況が続いている。肝細胞あるいは幹細胞由来肝様細胞の移植治療はこの状況を改善し得る有力な治療法と考えられるが、その有用性を検証できる動物モデルは確立されていない。本研究で用いた肝細胞キメラマウス作製系は、そのモデルとなり得るとともに、他家由来肝細胞移植に伴う免疫拒絶の病態解明、それに対する治療法確立のための有用なモデルともなり得る。
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