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Xenotransplantation from GalT-KO miniture swine to baboon in tolerance induction protocol

Research Project

Project/Area Number 20591900
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionNippon Medical School

Principal Investigator

SHIMIZU Akira  Nippon Medical School, 医学部, 准教授 (00256942)

Co-Investigator(Kenkyū-buntansha) MASUDA Yukinari  日本医科大学, 医学部, 講師 (70173755)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords腎臓移植 / 異種移植 / 拒絶反応 / 自然抗原ノックアウト / 心臓移植 / 急性拒絶反応 / 慢性拒絶反応 / 血栓性微小血管症 / 前臨床実験 / ヒヒ / 異腫移植
Research Abstract

Xenotransplantation could provide a solution to the critical shortage of organs for transplantation in humans. In attempt to prevent hyperacute rejection (HAR) and acute humoral xenograft rejection (AHXR), α1,3-galactosyltransferase gene knockout (GalT-KO) pigs have been produced in Massachusetts General Hospital, Boston, USA. In heart xenotransplantation from GalT-KO pig into baboon, heterotopic heart grafts could beat in abdominal cavity by 179 days (median 78 days). In kidney xenotransplantation, GalT-KO kidney grafts rejected by day 34 in chronic immunosuppression protocol, but grafts could survive up to 83 days in tolerance inducing protocol. GalT-KO heart and kidney xenografts did not develop hyperacute rejection. However, all GalT-KO heart and kidney grafts in the chronic immunosuppression group were rejected by AHXR with thrombotic microangiopathy. Acute cellular xenograft rejection (ACXR) and chronic rejection also developed. However, in the kidney grafts in tolerance inducing protocol, AHRX, ACXR, and chronic rejection could not be detected in the grafts. Therefore, we conclude that the tolerance inducing protocol is necessary for success the heart and kidney xenotransplantation from GalT-KO pig into baboons.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (30 results)

All 2011 2010 2009 2008

All Journal Article (22 results) (of which Peer Reviewed: 6 results) Presentation (8 results)

  • [Journal Article] Inhibition of matrix metalloproteinases reduces ischemia-reperfusion acute kidney injury.2011

    • Author(s)
      Kunugi S, Shimizu A, Kuwahara N, Du X, Takahashi M, Terasaki Y, Fujita E, Mii A, Nagasaka S, Akimoto T, Masuda Y, Fukuda Y
    • Journal Title

      Lab Invest

      Volume: 91 Pages: 170-180

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histopathology of xenografts in pig to non-human primate discordant xenotransplantation.2010

    • Author(s)
      Shimizu A, Yamada K
    • Journal Title

      Clin Transplant 24 Suppl 22

      Pages: 11-15

    • Related Report
      2010 Final Research Report
  • [Journal Article] Early humoral-mediated graft injuries in ABO-incompatible kidney transplantation in human beings.2010

    • Author(s)
      Sekijima M, Shimizu A, Ishii Y, Kudo S, Horita S, Nakajima I, Fuchinoue S, Teraoka S
    • Journal Title

      Transplant Proc 42

      Pages: 789-790

    • Related Report
      2010 Final Research Report
  • [Journal Article] Lymphangiogenesis associated with acute cellular rejection in rat liver transplantation.2010

    • Author(s)
      Ishii E, Shimizu A, Kuwahara N, Arai T, Kataoka M, Wakamatsu K, Ishikawa A, Nagasaka S, Fukuda Y
    • Journal Title

      Transplant Proc 42

      Pages: 4282-4285

    • Related Report
      2010 Final Research Report
  • [Journal Article] Inhibition of capillary repair in proliferative glomerulonephritis results in persistent glomerular inflammation with glomerular sclerosis.2010

    • Author(s)
      Masuda Y, Shimizu A, Kataoka M, Arai T, Ishikawa A, Du X, Saito SK, Aki K, Nagasaka S, Mii A, Fujita E, Fukuda Y
    • Journal Title

      Lab Invest 90

      Pages: 1468-1481

    • Related Report
      2010 Final Research Report
  • [Journal Article] Beneficial Effects of Perioperative Low-Dose Inhaled Carbon Monoxide on Pulmonary Allograft Survival in MHC-Inbred CLAWN Miniature Swine.2010

    • Author(s)
      Sahara H, Shimizu A, Setoyama K, Oku M, Okumi M, Nishimura H, Oriyanhan W, Tasaki M, Scalea J, Wada H, Bando T, Date H, Yamada K
    • Journal Title

      Transplantation 90

      Pages: 1336-1343

    • Related Report
      2010 Final Research Report
  • [Journal Article] Reversal of age-related thymic involution by an LHRH agonist in miniature swine.2010

    • Author(s)
      Hirakata A, Okumi M, Griesemer AD, Shimizu A, Nobori S, Tena A, Moran S, Arn S, Boyd RL, Sachs DH, Yamada K
    • Journal Title

      Transpl Immunol 24

      Pages: 76-81

    • Related Report
      2010 Final Research Report
  • [Journal Article] Prolonged survival of GalT-KO swine skin on baboons.2010

    • Author(s)
      Weiner J, Yamada K, Ishikawa Y, Moran S, Etter J, Shimizu A, Smith RN, Sachs DH
    • Journal Title

      Xenotransplantation 17

      Pages: 147-152

    • Related Report
      2010 Final Research Report
  • [Journal Article] Tolerance and long-lasting peripheral chimerism after allogeneic intestinal transplantation in MGH miniature swine.2010

    • Author(s)
      Ishikawa Y, Hirakata A, Griesemer AD, Etter J, Moran S, Weiner J, Shimizu A, Yamada K
    • Journal Title

      Transplantation 89

      Pages: 417-426

    • Related Report
      2010 Final Research Report
  • [Journal Article] Histopathology of xenografts in pig to non-human primate discordant xenotransplantation.2010

    • Author(s)
      Shimizu A, Yamada K
    • Journal Title

      Clin Transplant

      Volume: 24 Suppl22 Pages: 11-15

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Lymphangiogenesis associated with acute cellular rejection in rat liver transplantation2010

    • Author(s)
      Ishii E, Shimizu A, Kuwahara N, Arai T, Kataoka M, Wakamatsu K, Ishikawa A, Nagasaka S, Fukuda Y
    • Journal Title

      Transplant Proc

      Volume: 42 Pages: 4282-4285

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Results of gal-knockout porcine thymokidney xenografts.2010

    • Author(s)
      Griesemer AD, Hirakata A, Shimizu A, Moran S, Tena A, Iwaki H, Ishikawa Y, Schule P, Arn JS, Robson SC, Fishman JA, Sykes M, Sachs DH, Yamada K
    • Journal Title

      Transplantation 89

      Pages: 417-426

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Results of gal-knockout porcine thymokidney xenografts.2009

    • Author(s)
      Griesemer AD, Hirakata A, Shimizu A, Moran S, Tena A, Iwaki H, Ishikawa Y, Schule P, Arn JS, Robson SC, Fishman JA, Sykes M, Sachs DH, Yamada K
    • Journal Title

      Am J Transplant 9

      Pages: 2669-2678

    • Related Report
      2010 Final Research Report
  • [Journal Article] Upregulation of CD59 : potential mechanism of accommodation in a large animal model.2009

    • Author(s)
      Griesemer AD, Okumi M, Shimizu A, Moran S, Ishikawa Y, Iorio J, Arn JS, Yamada K
    • Journal Title

      Transplantation 87

      Pages: 1308-1317

    • Related Report
      2010 Final Research Report
  • [Journal Article] Upregulation of CD59 : potential mechanism of accommodation in a large animal model.2009

    • Author(s)
      Griesemer AD, Okumi M, Shimizu A, Moran S, Ishikawa Y, Iorio J, Arn JS, Yamada K.
    • Journal Title

      Transplantation 87

      Pages: 1308-1317

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] シクロスポリン腎毒性(シクロスポリン腎症)の進展過程における腎微小血管傷害2009

    • Author(s)
      清水章, 益田幸成
    • Journal Title

      今日の移植 22

      Pages: 667-673

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Rejection of cardiac xenografts transplanted from a1,3-galactosyltransferase gene-knockout (GalT-KO) pigs to baboons.2008

    • Author(s)
      Hisashi Y, Yamada K, Kuwaki K, Tseng Y-L, Dor FJMF, Houser SL, Robson SC, Schuurman H-J, Cooper DKC, Sachs DH, Colvin RB, Shimizu A
    • Journal Title

      Am J Tranplant 8

      Pages: 2516-2526

    • Related Report
      2010 Final Research Report
  • [Journal Article] Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alpha1,3-galactosyltransferase gene-knockout pigs in baboons.2008

    • Author(s)
      Shimizu A, Hisashi Y, Kuwaki K, Tseng YL, Dor FJ, Houser SL, Robson SC, Schuurman HJ, Cooper DK, Sachs DH, Yamada K, Colvin RB
    • Journal Title

      Am J Pathol 172

      Pages: 1471-1481

    • Related Report
      2010 Final Research Report
  • [Journal Article] Pigislet xenograft rejection in a mouse model with an established human immune system.2008

    • Author(s)
      Tonomura N, Shimizu A, Wang S, Yamada K, Tchipashvili V, Weir GC, Yang YG
    • Journal Title

      Xenotransplantation 15

      Pages: 129-135

    • Related Report
      2010 Final Research Report
  • [Journal Article] Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model.2008

    • Author(s)
      Tonomura N, Habiro K, Shimizu A, Sykes M, Yang YG
    • Journal Title

      Blood 111

      Pages: 4293-4296

    • Related Report
      2010 Final Research Report
  • [Journal Article] Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alphal, 3-galactosyltransferase gene-knockoutpigs in baboons2008

    • Author(s)
      Shimizu A, Hisashi Y, Kuwaki K, Tseng YL, Dor FJ, Houser SL, Robson SC, Schuurman HJ, Cooper DK, Sachs DH, Yamada K, Colvin RB
    • Journal Title

      Am J Pathol 172

      Pages: 1471-1481

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rejection of cardiac xenografts transplanted from alphal, 3-galactosyl-transferase gene-knockout (GalT-KO)pigs to baboons2008

    • Author(s)
      Hisashi Y, Yamada K, Kuwaki K, Tseng YL, Dor FJ, Houser SL, Robson sc, Schuurman HJ, Cooper DK, Sachs DH, Colvin RB, Shitnizu A.
    • Journal Title

      Am J Transplant 8

      Pages: 2516-2526

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] The pathological characteristics of acute antibody-mediated rejection in DA to Lewis ratorthotopic liver transplantation2010

    • Author(s)
      Shimiuz A, Ishii E, Kuwahara N, Arai T, Kataoka M, Fukuda Y
    • Organizer
      XXIII International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-08-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] Acute kidney injury during hepatic failure in rats.2010

    • Author(s)
      Shimizu A, Ishii E, Ishikawa A, Arai T, Kuwahara N, Masuda Y, Nagasaka S, Fukuda Y
    • Organizer
      2010 Renal Week in Denver
    • Place of Presentation
      Colorado
    • Related Report
      2010 Final Research Report
  • [Presentation] The pathological characteristics of acute antibody-mediated rejection in DA to Lewis rat orthotopic liver transplantation.2010

    • Author(s)
      Shimizu A, Ishii E, Kuwahara N, Arai T, Kataoka M, Fukuda Y
    • Organizer
      XXIII International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver
    • Related Report
      2010 Final Research Report
  • [Presentation] Chronic antibody-mediated rejection in rat orthotopic liver transplantation.2010

    • Author(s)
      Ishii E, Shimizu A, Arai T, Kataoka M, Ishikawa A, Wakamatsu K, Nagasaka S, Fukuda Y
    • Organizer
      XXIII International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver
    • Related Report
      2010 Final Research Report
  • [Presentation] Lymhangiogenesis associated with acute cellular rejection in rat liver transplantation.2010

    • Author(s)
      Ishii E, Shimizu A, Kuwahara N, Arai T, Kataoka M, Wakamatsu K, Ishikawa A, Nagasaka S, Fukuda Y
    • Organizer
      XXIII International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver
    • Related Report
      2010 Final Research Report
  • [Presentation] 大動物からヒトへの臨床応用:αGa1ノックアウトMGHミニブタからヒヒへの異種腎移植の病理像2009

    • Author(s)
      清水章
    • Organizer
      移植腎病理研究会・第13回学術集会
    • Place of Presentation
      東京
    • Year and Date
      2009-07-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] 腎移植の新しい治療戦略:大動物からヒトへの臨床応用,aGalノックアウトMGHミニブタからヒヒへの異種腎移植の病理像,2009

    • Author(s)
      清水章
    • Organizer
      移植腎病理研究会・第13回学術集会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] The pathological characteristics of acute antibody-mediated rejection in DA to Lewis rat orthotopic liver transplantation.2009

    • Author(s)
      Shimiuz A, Ishii E, Kuwahara N, Arai T, Kataoka M, Fukuda Y
    • Organizer
      The American Transplant Congress.
    • Place of Presentation
      Boston
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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