The generation of clone pigs expressing blood group antigens -developing a tolerance induction method-

• Project/Area Number: 18380162
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied animal science
• Research Institution: Obihiro University of Agriculture and Veterinary Medicine
• Principal Investigator: OGAWA Haruko Obihiro University of Agriculture and Veterinary Medicine, 原虫病研究センター, 准教授 (10400079)
• Co-Investigator(Kenkyū-buntansha): OHNISHI Akira 独立行政法人農業生物資源研究所, 遺伝子組換え家畜研究センター, 上級研究員 (30414890) ; KOBAYASHI Takaaki 名古屋大学, 医学部, 教授 (70314010)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥10,440,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥1,140,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2006: ¥5,500,000 (Direct Cost: ¥5,500,000)
• Keywords: 移植 / 拒絶反応 / 免疫寛容 / 血液型抗原 / クローン動物 / 核移植 / リンパ球 / ABO

Research Abstract

本研究の目標は、ABO不適合移植の患者における拒絶反応のリスクを低減するために、免疫寛容誘導法を確立する事である。マウス実験で得られた結果を、ヒトにより近い実験動物を用いて確認するために、ヒトのABO式血液型を発現するブタ実験モデルを用いた研究の推進を目指している。現在、ヒトの血液型抗原を生成する酵素遺伝子を導入したブタ細胞の核を用いて、ヒトのABO式血液型を発現する遺伝子改変クローンブタを作出している。

Research Products

• [Journal Article] Removal of blood group A/B antigen in organs by ex vivo and in vivo administration of endo-β-galactosidase (Abase) for ABO incompatible transplantation (2009)
  • Author(s): Kobayashi T, Liu D, Ogawa H, Miwa Y, Nagasaka T, Maruyama S, Li YT, Onishi A, Iwamoto M, Kuzuya T, Kadomatsu K, Uchida K, Nakao A
  • Journal Title: Transplant Immunology 20 Pages: 132-138
  • Peer Reviewed
• [Journal Article] Removal of blood grollp A/B antigen in organs by ex vivo and in vivo administration of endo-β-galactosidase (ABase)for ABO incompatible transplantation (2009)
  • Author(s): Kobayashi T, Liu D, Ogawa H, Miwa Y, Nagasaka T, Maruyama S, Li YT, Onishi A, Iwamoto M, Kuzuya T, Kadomatsu K, Uchida K, Nakao A
  • Journal Title: Transplant Immunology 20 Pages: 132-138
  • Peer Reviewed
• [Journal Article] Alternative strategy for overcoming ABO incompatibility (2007)
  • Author(s): Kobayashi T, Liu DG, Ogawa H, Miwa Y, Nagasaka T, Maruyama S, Li YT, Onishi A, Kuzuya T, Kadomatsu K, Uchida K, Nakao A
  • Journal Title: Transplantation 83 Pages: 1284-1286
  • Peer Reviewed
• [Journal Article] Alternative strategy for overcoming ABO incompatibility (2007)
  • 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
  • Journal Title: Transplantation 83 Pages: 1284-1286
  • Peer Reviewed
• [Journal Article] Prophylactic treatment of antibody-mediated rejection with high-dose mizoribine and pharmacokinetic study (2007)
  • Author(s): Liu D, Kobayashi T, Nagasaka T, Miwa Y, Ma Y, Yokoyama I, Kuzuya T, Oikawa T, Morozumi K, Uchida K, Nakao A
  • Journal Title: Transplant International 30 Pages: 365-370
  • Peer Reviewed
• [Journal Article] Alternative strategy for overcoming ABO incompatibility. (2007)
  • Author(s): Kobayashi T., Liu D.G., Ogawa H., Miwa Y., Nagasaka T., Maruyama S., Li Y.T., Onishi A., Kuzuya T., Kadomatsu K., Uchida K., Nakao A.
  • Journal Title: Transplantation 83 Pages: 1284-1286
• [Journal Article] Profiling terminal N-acetyllactosamines of glycans on mammalian cells by an immuno-enzymatic assay (2006)
  • Author(s): Ogawa H, Galili U
  • Journal Title: Glycoconjugate J. 23 Pages: 663-674
  • Peer Reviewed
• [Journal Article] A series of surveys on assay for anti-A/B antibody by Japanese Society for ABO incompatible transplantation (2006)
  • Author(s): Kobayashi T, Saito K
  • Journal Title: Xenotransplantation 13 Pages: 136-140
  • Peer Reviewed
• [Journal Article] Transmission of mitochondrial DNA in pigs and progeny derived from nuclear transfer of Meishan pig fibroblast cells (2006)
  • Author(s): Takeda K, Tasai M, Iwamoto M, Akita T, Tagami T, Nirasawa K, Hanada H, Onishi A
  • Journal Title: Mol. Reprod. Dev 73 Pages: 306-312
  • Peer Reviewed
• [Journal Article] ABO 血液型不適合移植攻略のための新補助療法 (2006)
  • Author(s): 小林孝彰
  • Journal Title: 移植 41 Pages: 573-576
  • NAID: 10024371400
• [Journal Article] Profiling terminal N-acetyllactosamines of glycans on mammalian cells by an immuno-enzymatic assay. (2006)
  • Author(s): Ogawa H, Galili U.
  • Journal Title: Glycoconjugate J. 23 Pages: 663-674
• [Presentation] Tolerance Induction to ABO blood group antigens by using autologous lymphocytes engineered to express the cognate antigen (2008)
  • Author(s): Ogawa H
  • Organizer: XXII International Congress of the Transplantation Society
  • Place of Presentation: Sydney (Australia)
• [Presentation] Induction of B cell tolerance to incompatible ABO Blood group antigens in transplantation (2007)
  • Author(s): Ogawa H
  • Organizer: IPTA-IXA 2007 Joint conference
  • Place of Presentation: Minneapolis (USA)
• [Presentation] Successful removal of blood group A/B antigen in organs by ex vivo and invivo administration of endo-beta-galactosidase (Abase) (2007)
  • Author(s): Kobayashi T
  • Organizer: IPTA-IXA 2007 Joint conference
  • Place of Presentation: Minneapolis (USA)
• [Presentation] Reduction of Blood Group A/B Antigen Expression in Organ by In Vivo Infusion of endo-β-Galactosidase (2007)
  • Author(s): Kobayashi T
  • Organizer: American Transplant Congress 2007
  • Place of Presentation: San Francisco (USA)
• [Presentation] Induction of B cell tolerance to incompatible ABO blood group antigens in transplantation (2007)
  • Author(s): Ogawa H
  • Organizer: Keystone Symposium for Biology of B cells in Health and Diseases
  • Place of Presentation: Banff (Canada)
• [Presentation] Induction of B cell tolerance to incompatible ABO Blood group antigens in transplantation (2007)
  • Author(s): Ogawa H, Galili U
  • Organizer: IPTA-IXA 2007 Joint conference
  • Place of Presentation: Minneapolis(USA)
• [Presentation] Successful removal of blood group A/B antigen in organs by ex vivo and in vivo administration of endo-beta-galactosidase(ABasse) (2007)
  • Author(s): Kobayashi T, Ogawa H, Liu D, Nagasaka T, Miwa Y, Katayama A, Maruyama S, Li Y-T, Onishi A, Uchida K
  • Organizer: IPTA-IXA 2007 Joint conference
  • Place of Presentation: Minneapolis(USA)
• [Presentation] Reduction of Blood Group A/B Antigen Expression in Organ by In Vivo Infusion of endo-β-Galactosidase. (2007)
  • Author(s): Kobayashi T, Liu DG, Ogawa H, Miwa Y, Nagasaka T, Maruyama S, Li Y-T, Onishi A, Kuzuya T, Kadomatsu K, Uchida K, Nakao A
  • Organizer: American Transplant Congress 2007
  • Place of Presentation: San Francisco(USA)
• [Presentation] Pig kidney expressing both endo-beta-galactosidase C and hDAF prevented hyperacute rejection in baboon without antibody removal (2007)
  • Author(s): Kobayashi T, Onishi A, Liu D, Nagasaka T, Miwa Y, Katayama A, Maruyama S, Iwamoto M, Uchida K, Nakao A
  • Organizer: IPTA-IXA 2007 Joint conference
  • Place of Presentation: Minneapolis(USA)
• [Presentation] Significance of human DAF and thrombomodulin gene transfer for coagulation control in pig to human xenotransplantation (2007)
  • Author(s): Miwa Y, Yamamoto K, Katayama A, Nagasaka T, Onishi A, Iwamoto M, Kadomatsu K, Uchida K, Nakao A, Kobayashi T
  • Organizer: IPTA-IXA 2007 Joint conference
  • Place of Presentation: Minneapolis(USA)
• [Presentation] Related versus unrelated living donor ABO-lncompatible kidney transplantation: Are spousal living donors a good source of kidneys for ABO-incompatible living transplantation? (2007)
  • 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)
• [Presentation] Beneficial effect of human DAF and thrombomodulin expression in pig endothelial cells on coagulation control (2007)
  • Author(s): Miwa Y, Kobayashi T, Yamamoto K, Nagasaka T, Liu DG, Kuzuya T, Onishi A, Kadomatsu K, Uchida K, Nakao A
  • Organizer: American Transplant Congress 2007
  • Place of Presentation: San Francisco(USA)
• [Presentation] ABO 血液型不適合移植戦略のための新補助療法 (2006)
  • Author(s): 小林孝彰
  • Organizer: 第42回日本移植学会総会
• [Book] ABO血液型不適合移植の新戦略-2008- (2008)
  • Author(s): 小林孝彰, 齋藤和英
  • Publisher: 日本医学館
• [Book] ABO血液型不適合移植の新戦略-2007- (2007)
  • Author(s): 小林孝彰, 齋藤和英
  • Publisher: 日本医学館
• [Book] ABO血液型不適合移植の新戦略-2006- (2007)
  • Author(s): 小林孝彰, 齋藤和英
  • Publisher: 日本医学館
• [Book] ABO血液型不適合移植の新戦略-2007- (2007)
  • Author(s): 小林孝考、齋藤和英
  • Total Pages: 86
  • Publisher: 日本医学館