| Project/Area Number |
02404050
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
MITO Michio Asahikawa Medical College, Vice President, 副学長 (60000981)
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| Co-Investigator(Kenkyū-buntansha) |
INAGAKI Mitsuhiro Asahikawa Medical College, Fellow, 医学部, 助手 (80261410)
SAKATA Hiromi Asahikawa Medical College, Fellow, 医学部, 助手 (50235157)
ONODERA Kazuhiko Asahikawa Medical College, Fellow, 医学部, 助手 (00204264)
KUSANO Mitsui Asahikawa Medical College, Associate Professor, 医学部, 講師 (70091569)
KASAI Shinichi Asahikawa Medical College, Associate Professor, 医学部, 助教授 (40091566)
菅原 睦 旭川医科大学, 医学部, 助手 (40226428)
江端 英隆 旭川医科大学, 医学部, 助教授 (20091564)
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| Project Period (FY) |
1990 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥17,100,000 (Direct Cost: ¥17,100,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1992: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1990: ¥9,400,000 (Direct Cost: ¥9,400,000)
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| Keywords | Hepatocyte transplantation / Intrasplenic transplantation / Monoclonal antibody / Hepatocyte growth factor / Cryopreservation / Human hepatocyte / Electroporation / Retrovirus-vector / 免疫抑制 / 細胞接着因子 / 先天性代謝異常症 / 遺伝子導入 / 異種移植 / Hepatocyte Growth Factor / Hepatocyte Groth Factor / 脾内移植 / 脾内肝細胞移植 / 無アルブミンラット / レトロウイルス / 外来遺伝子導入 / 分離肝細胞 / growth factor / 胎児肝細胞 / レトロウィルス / 外来遺伝子 / 異所性肝組織 |
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| Research Abstract |
The advantages of cellular transplantation are : 1) requires no vascular anastomosis, 2) autotransplantation is applicable, 3) complicated and hazardous immunosuppressive drugs are not necessary with autotransplantation, 4) long-term cryopreservation is possible, and 5) gene therapy is easily applied.
Our success with long survival of transplantated rat and monkey hepatocytes in the spleen and development of a preparation of isolated human hepatocytes has renewed interests in clinical trials of hepatocyte transplantation (HCTX). In several cases, we have observed the fate of human hepatocytes in the spleen for a long period. So far, we detected inoculated hepatocytes in the spleen, but there little evidence that inoculated hepatocytes can proliferate and occupy the large area of the spleen in man.
In basic experiments, we evaluated the beneficial effects of exogenous growth factors on proliferation of inoculated hepatocytes in the spleen and immuno-modulation using monoclonal antibodies for cell-surface antigens. And also, advances in gene-engineering enable us to do exogenous gene-transfer to isolated hepatocytes by electroporation and retrovirus-vector. Gene transfection and subsequent HCTX need to be promotion, but several fundamental problems remain unresolved : 1) whether or not human hepatocytes can proliferate in vivo, and if proliferate, how long do inoculated hepatocytes maintain their hepatic function? , 2) where is the most suitable inoculation site? , and 3) development of the method for exogenous gene-transfection into human hepatocytes and control of the expression leve of transfected gene in hepatocytes.
Basic experiments to solve these problems must be accelerated fully, and HCTX with geneengineering will become one choice of the treatments for liver diseases.
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