| Project/Area Number |
14570975
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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 |
Hematology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
ITOH Katsuhiko Kyoto University, Faculty of Medicine, Lecturer, 医学研究科, 講師 (90281097)
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| Co-Investigator(Kenkyū-buntansha) |
HIGASHITSUJI Hiroaki Kyoto University, Faculty of Medicine, Assistant, 医学研究科, 助手 (60281094)
FUJITA Jun Kyoto University, Faculty of Medicine, Professor, 医学研究科, 教授 (50173430)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Hematopoietic stem cell / retroviral vector / hepatocyte / hepatocyte / bone marrow / stem cell / retrovirus / vector / レトロウイルスベクター |
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| Research Abstract |
Recent report indicated that the hematopoietic stem cells can trans-differentiate into hepatocytes, neurons, muscle cells or epitherial cells and these cells are the candidate of the target cells in the gene therapy.
We have proved that the transduced hematopoietic stem cells by the retroviral vectors carrying anti-cancer drug resistant gene (MGMT/P14OK) could be enriched in vivo and that the almost 100% of periferal blood cells were replaced by the transduced cells. On the other hand, after the replacement, only a small proportion of the hepatocytes (a few cells per 100,000-1,000,000 cells) was confirmed to be derived from transduced hematopoietic cells. Thus, we have concluded that the proportion of the hematopoietic cells is very low, which would trans-differentiate into hepatocyte in vivo.
We have proved that the FMEV-type of the retroviral vectors were superior to those based on MoMLV in the expression of transgene in the liver. Furthermore, we have developed novel vectors (SF-Hep3 and SF-Hep5) by engineering the U3 region of the LTR, which provided efficient transgene expression in hepatocytes in vivo.
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