2007 Fiscal Year Final Research Report Summary
Antigen removal in grafts and induction of accommodation for overcoming ABO incompatibility
| Project/Area Number |
18591407
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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 |
General surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
KOBAYAHSI Takaaki Nagoya University, School of Medicine, Professor (70314010)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Koji Nagoya University, University Hospital, Associate Professor (90362251)
TAKEDA Shin Nagoya University, Graduate School of Medicine, Associate Professor (20314015)
ONISHI Akira National Institute of Agrobiological Sciences, Group Director (30414890)
MARUYAMA Shoichi Nagoya University, Hospital, Associate Professor (10362253)
OGAWA Haruko Obihiro University of Agriculture and Veterinary Medicine, National Research Center for Protozoan Diseases, Associate Professor (10400079)
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| Project Period (FY) |
2006 – 2007
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| Keywords | ABO blood group / Antigen / Antibody / Antibody-mediated rejection / Accommodation / Endo-β-galactosidase / Organ transplantation |
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| Research Abstract |
We attempted to develop the comprehensive treatment to overcome ABO incompatibility which is a high risk factor for antibody-mediated rejection in organ transplantation. (1) Recombinant ABase(rABase) derived from clostridium perfringens, which effectively releases A/B antigen, was produced in E. coil BL-21. rABase removed about 90% of A antigen(Ag) and B Ag on human RBC. In vivo infusion of rABase into a blood type A baboon demonstrated a marked reduction(87-97%) of A Ag in the kidney and liver. Excised baboon kidney(Blood type B) was perfused with cold UW solution +/-purified rABase and then preserved 4h at 4℃. B Ag in glomeruli were reduced to 49% at 1h and 6% at 4h. A novel strategy was suggested using ABase would include enzymatic digestion of AB Ag during cold storage after organ retrieval and/or repeated in vivo infusion into the recipient until accommodation developed. (2) Human decay accelerating factor(hDAF) and thrombomodulin genes were introduced into porcine aortic endothelial cells. The capacity of activated protein C production, clotting time of human plasma and mRNA of Tissue Factor and Plasminogen Activator Inhibitor-1 were investigated. Inhibition of endothelial activation by complement regulatory protein and control of coagulation by thrombomodulin are considered to be essential for both prevention of rejection and induction of accommodation. (3) We established the assay to determine stimulation index(S.I) for cell cycle-related protein mRNA expression as immune function monitoring. We are planning to elucidate the significance of monitoring by measuring the blood from the recipients after transplantation.
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[Journal Article] Relation between human decay-accelerating factor(hDAF) expression in pig cells and inhibition of human serum anti-pig cytotoxicity: value of highly expressed hDAF for xenotransplantation2007
Author(s)
Liu. D, Kobayashi T, Onishi A, Furusawa T, Iwamoto T, Suzuki S, Miwa Y, Nagasaka T, Maruyama S, Kadomatsu K, Uchida K, Nakao A
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Journal Title
Xenotransplantation 14
Pages: 67-73
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Prophylactic treatment of antibody-mediated rejection with high-dose mizoribine and pharmacokinetic study2007
Author(s)
Liu D, Kobayashi T, Nagasaka T, Miwa Y, Ma Y, Yokoyama I, Kuzuya T, Oikawa T, Morozumi K, Uchida K, Nakao A.
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Journal Title
Transplant International 30
Pages: 365-370
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Alternative strategy for overcoming ABO incompatibility2007
Author(s)
Kobayashi T, Liu D, Ogawa H, Miwa Y, Nagasaka T, Maruyama S, LiY-T, Onishi A, Kuzuya T, Kadomatsu K, Uchida K, Nakao A.
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Journal Title
Transplantation 83
Pages: 1284-1286
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Relation between human decay-accelerating factor (hDAF) expression in pig cells and inhibition of human serum anti-pig cytotoxicity : value of highly expressed hDAF for xenotransplantation2007
Author(s)
Liu. D, Kobayashi, T, Onishi, A, Furusawa, T, Iwamoto, T, Suzuki, S, Miwa, Y, Nagasaka, T, Maruyama, S, Kadomatsu, K, Uchida, K, Nakao, A
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Journal Title
Xenotransplantation 14
Pages: 67-73
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Prophylactic treatment of antibody-mediated rejection with high-dose mizoribine and pharmacokinetic study2007
Author(s)
Liu, D, Kobayashi, T, Nagasaka, T, Miwa, Y, Ma, Y, Yokoyama, I, Kuzuya, T, Oikawa, T, Morozumi, K, Uchida, K, Nakao, A
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Journal Title
Transplant International 30
Pages: 365-370
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Alternative strategy for overcoming ABO incompatibility2007
Author(s)
Kobayashi, T, Liu, D, Ogawa, H, Miwa, Y, Nagasaka, T, Maruyama, S, Li, Y-T, Onishi, A, Kuzuya, T, Kadomatsu, K, Uchida, K, Nakao, A
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Journal Title
Transplantation 83
Pages: 1284-1286
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Intrarenal administration of recombinant human soluble thrombomodulin ameliorates ischaemic acute renal failure2007
Author(s)
Ozaki, T, Anas, C, Maruyama, S, Yamamoto, T, Yasuda, K, Morita, Y, Ito, Y, Gotoh, M, Yuzawa, Y, Matsuo, S
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Journal Title
Nephrol Dial Transplant 23
Pages: 110-119
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Establishment of pharmacodynamic monitoring of MMF-Comparison between MTT assay and flow cytometry-2006
Author(s)
Yoko, Kurata, Takafumi, Kuzuya, Takaaki, Kobayashi, Yuko, Miwa, Kazuharu, Uchida, Akimasa, Nakao, Hiroyuki, Kamei, Kazuhisa, Matsuba, Toshitaka, Nabeshima
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Reduction of Blood Group A/B Antigen Expression in Organ by In Vivo Infusion of endo-β-Galactosidase.2007
Author(s)
Kobayashi T, DaGe Liu, Ogawa H, Miwa Y, Nagasaka T, Maruyama S, Yu-The Li, Onishi A, Kuzuya T, Kadomatsu K, Uchida K, Nkao A
Organizer
American Transplant Congress 2007
Place of Presentation
San Francisco(USA)
Year and Date
20070522-27
Description
「研究成果報告書概要(和文)」より
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[Presentation] Related Versus Unrelated Living Donor ABO-Incompatible Kidney Transplantation : Are Spousal Living Donors a Good Source of Kidneys for ABO-Incompatible Living Transplantation2007
Author(s)
Uchida, K, Katayama, A, Nagasaka, T, Goto, N, Morozumi, K, Takeda, A, Goto, Y, Kobayashi, T, Nakao, A
Organizer
American Transplant Congress 2007
Place of Presentation
San Francisco (USA)
Year and Date
20070522-27
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Reduction of Blood Group A/B Antigen Expression in Organ by In Vivo Infusion of endo- β-Galactosidase2007
Author(s)
Kobayashi, T, DaGe, Liu, Ogawa, H, Miwa, Y, Nagasaka, T, Maruyama, S, Yu-The, Li, Onishi, A, Kuzuya, T, Kadomatsu, K, Uchida, K, Nkao, A
Organizer
American Transplant Congress 2007
Place of Presentation
San Francisco (USA)
Year and Date
20070522-27
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Beneficial Fffect of Human DAF and Thrombomodulin Expression in Pig Endothelial Cells on Coagulation Control2007
Author(s)
Miwa, Y, Kobayashi, T, Yamamoto, K, Nagasaka, T, DaGe, Liu, Kuzuya, T, Onishi, A, Kadomatsu, K, Uchida, K, Nakao, A
Organizer
American Transplant Congress 2007
Place of Presentation
San Francisco (USA)
Year and Date
20070522-27
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Alternative strategy for overcoming ABO incompatibility2006
Author(s)
Kobayashi T, Liu D, Miwa Y, Ogawa H, Kadomatsu K, Li Y-T, Nagasaka T, Maruyama S, Kuzuya T, Onishi A, Uchida K, Nakao A
Organizer
World Transplant Congress 2006
Place of Presentation
Boston(USA)
Year and Date
20060722-27
Description
「研究成果報告書概要(和文)」より
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[Presentation] Relation between hDAF expression level in pig cells and inhibition of human serum anti-pig cytotoxicity2006
Author(s)
Liu D, Kobayashi T, Onishi A, Furusawa T, Iwamoto M, Suzuki S, Miwa Y, Nagasaka T, Maruyama S, Uchida K, Nakao A.
Organizer
World Transplant Congress 2006
Place of Presentation
Boston(USA)
Year and Date
20060722-27
Description
「研究成果報告書概要(和文)」より
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[Presentation] Alternative strategy for overcoming ABO incompatibility2006
Author(s)
Kobayashi, T, Liu, D, Miwa, Y, Ogawa, H, Kadomatsu, K, Li, Y-T, Nagasaka, T, Maruyama, S, Kuzuya, T, Onishi, A, Uchida, K, Nakao, A
Organizer
World Transplant Congress 2006
Place of Presentation
Boston (USA)
Year and Date
20060722-27
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Relation between hDAF expression level in pig cells and inhibition of human serum anti-Dig cytotoxirity2006
Author(s)
Liu, D, Kobayashi, T, Onishi, A, Furusawa, T, Iwamoto, M, Suzuki, S, Miwa, Y, Nagasaka, T, Maruyama, S, Uchida, K, Nakao, A
Organizer
World Transplant Congress 2006
Place of Presentation
Boston (USA)
Year and Date
20060722-27
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Excellent outcome in ABO-incompatible living donor kidney transplantation with the modified immunosuppression : the useof basiliximab/cyclophosphamide instead of antilymphocyte globulin/cyclophosnhamide2006
Author(s)
Uchida, K, Katayama, A, Nagasaka, T, Goto, N, Takeda, A, Morozumi, K, Kobayashi, T, Nakao, A
Organizer
World Transplant Congress 2006
Place of Presentation
Boston (USA)
Year and Date
20060722-27
Description
「研究成果報告書概要(欧文)」より
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