• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Attenuation of hyperacute dysfunction and coagulopathy in GalT-KO pulmonary xenotransplantation

Research Project

Project/Area Number 23390337
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionKagoshima University

Principal Investigator

SAHARA Hisashi  鹿児島大学, 医用ミニブタ・先端医療開発研究センター, 准教授 (90452333)

Co-Investigator(Kenkyū-buntansha) YAMADA Kazuhiko  鹿児島大学, 医用ミニブタ・先端医療開発研究センター, 教授 (40241103)
NAGASHIMA Hiroshi  明治大学, 農学部, 教授 (50318664)
DATE Hiroshi  京都大学, 医学(系)研究科(研究院), 教授 (60252962)
Co-Investigator(Renkei-kenkyūsha) SHIMIZU Akira  日本医科大学, 医学部, 教授 (00256942)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2011: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywordsトランスレーショナルリサーチ / 異種肺移植 / GalT-KOブタ / カニクイザル / 一酸化炭素 / 急性期肺機能不全 / 移植・再生医療 / Ex-vivo灌流 / CalT-KOブタ / 血小板 / 肺血管抵抗
Research Abstract

The results of both heart and kidney GalT-KO swine-to-primate studies have been more encouraging than for lung xenotransplantation. This may be because research in pulmonary xenotransplantation is limited. Here, we evaluated 1) whether GalT-KO lungs could prevent hyper-acute pulmonary xenograft dysfunction using ex-vivo lung perfusion or in-vivo orthotopic left lung transplant model and 2) the effect of carbon monoxide (CO) on reducing the development of microangiopathy (CO-treated animals). GalT-KO lungs exhibited stable pulmonary function compared with wild-type lungs when perfused with human blood in an ex-vivo perfusion model, which was confirmed by the in-vivo transplant model. Although, thrombotic microangiopathy ultimately developed in all grafts of the CO-treated animals, the degree of microangiopathy was reduced in these animals. Reduction of the innate immune response by CO treatment would be one of the therapeutic strategies for prolonging pulmonary xenograft survival.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (32 results)

All 2014 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 6 results) Presentation (20 results) Remarks (2 results)

  • [Journal Article] Production of cloned NIBS (Nippon Institute for Biological Science) and α-1, 3-galactosyltransferase knockout MGH miniature pigs by somatic cell nuclear transfer using the NIBS breed as surrogates2013

    • Author(s)
      Shimatsu Y, Yamada K, Horii W, Hirakata A, Sakamoto Y, Waki S, Sano J, Saitoh T, Sahara H, Shimizu A, Yazawa H, Sachs DH, Nunoya T
    • Journal Title

      Xenotransplantation

      Volume: 20(3) Issue: 3 Pages: 157-64

    • DOI

      10.1111/xen.12031

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The induction of tolerance of renal allografts by adoptive transfer in miniature Swine2013

    • Author(s)
      Okumi M, Scalea JR, Gillon BC, Tasaki M, Villani V, Cormack T, Hirakata A, Shimizu A, Sachs DH, Yamada K.
    • Journal Title

      American Journal of Transplantation

      Volume: 13 Issue: 5 Pages: 1193-1202

    • DOI

      10.1111/ajt.12194

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current progress in xenogeneic tolerance2012

    • Author(s)
      Yamada K, Scalea J
    • Journal Title

      Curr Opin Organ Transplant

      Volume: 17(2) Issue: 2 Pages: 168-73

    • DOI

      10.1097/mot.0b013e32835090f6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Current progress in xenogeneic tolerance.2012

    • Author(s)
      Yamada K, Scalea J.
    • Journal Title

      Current Opinion in Organ Transplantation

      Volume: 17 Pages: 168-173

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ドナー臓器の機能評価および修復を可能とする常温体外肺循環回路(EVLP)下での一酸化炭素吸入療法によるミニブタ移植肺生着延長効果の検討2012

    • Author(s)
      佐原寿史、脇 詩織、関島光裕、三浦宏平、河合昭浩、清水 章、山田和彦
    • Journal Title

      今日の移植

      Volume: 25 Pages: 495-499

    • Related Report
      2012 Annual Research Report
  • [Journal Article] ドナーに対する一酸化炭素吸入療法による移植肺生着延長効果:前臨床ミニブタモデルを用いた新たな臓器保存方法への発展2012

    • Author(s)
      佐原寿史、山田和彦
    • Journal Title

      Organ Biology

      Volume: 19 Pages: 11-14

    • NAID

      130004710024

    • Related Report
      2012 Annual Research Report
  • [Journal Article] T-cell-mediated immunological barriers to xenotransplantation2012

    • Author(s)
      Scalea J, Hanecamp I, Robson SC, Yamada K
    • Journal Title

      Xenotransplantation

      Volume: 19 Pages: 23-30

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 異種臓器移植の臨床応用をめざして-前臨床異種移植はここまで進んでいる2011

    • Author(s)
      山田和彦, 佐原寿史
    • Journal Title

      医学のあゆみ

      Volume: 237(5) Pages: 559-66

    • URL

      http://www.ishiyaku.co.jp/magazines/ayumi/AyumiArticleDetail.aspx?BC=286290&AC=10269

    • Related Report
      2013 Final Research Report
  • [Journal Article] 異種臓器移植の臨床応用をめざして-前臨床異種移植はここまで進んでいる2011

    • Author(s)
      山田和彦、佐原寿史
    • Journal Title

      医学のあゆみ

      Volume: 237(5) Pages: 559-566

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Autoimmune sensitization to cardiac myosin leads to acute rejection of cardiac allografts in miniature swine2011

    • Author(s)
      Veillette GR, Sahara H, Meltzer AJ, Weiss MJ, Iwamoto y Kim KM, Rosengard BR, Allan JS, Houser SL, Sachs DH, Benichou G, Madsen JC
    • Journal Title

      Transplantation

      Volume: 91(11) Issue: 11 Pages: 1187-1191

    • DOI

      10.1097/tp.0b013e318218415d

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] シンポジウム「肺移植の現況と将来展」GalT-KO ブタ・カニクイザル間異種肺移植実験の現状 -異種腎臓移植との比較による治療標的の解明と対策2014

    • Author(s)
      佐原寿史, 山田和彦
    • Organizer
      第31回日本呼吸器外科学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム「肺移植の現況と将来展」GalT-KOブタ・カニクイザル間異種肺移植実験の現状 - 異種腎臓移植との比較による治療標的の解明と対策.2014

    • Author(s)
      佐原寿史、山田和彦
    • Organizer
      第31回日本呼吸器外科学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Attenuation of hyperacute dysfunction and microangiopathy by the treatment of carbon monoxide in GalT-KO pulmonary xenotransplantation2013

    • Author(s)
      Sahara H, Nagashima H, Miura K, Waki S, Kawai A, Nakano K, Matsunari H, Arai Y, Sekijima M, Tasaki M, Setoyama K, Shimizu A, Date H, Yamada K
    • Organizer
      12th Congress IXA (International Xenotransplantation Association 2013)
    • Place of Presentation
      Osaka
    • Related Report
      2013 Final Research Report
  • [Presentation] Attenuation of hyperacute dysfunction and coagulopathy in GalT-KO pulmonary xenotransplantation2013

    • Author(s)
      Sahara H, Nagashima H, Sekijima M, Tasaki M, Setoyama K, Matsunari H, Nakano K, Date H, Shimizu A, Yamada K
    • Organizer
      The 13th Congress of the Asian Society of Transplantation
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Attenuation of hyperacute dysfunction and coagulopathy in GalT-KO pulmonary xenotransplantation.2013

    • Author(s)
      Sahara H, Nagashima H, Sekijima M, Tasaki M, Setoyama K, Matsunari H, Nakano K, Date H, Shimizu A, Yamada K
    • Organizer
      The 13th Congress of the Asian Society of Transplantation
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Annual Research Report
  • [Presentation] Attenuation of hyperacute dysfunction and microangiopathy by the treatment of carbon monoxide in GalT-KO pulmonary xenotransplantation2013

    • Author(s)
      Kawai A, Nakano K, Matsunari H, Arai Y, Sekijima M, Tasaki M, Setoyama K, Shimizu A, Date H, Yamada K
    • Organizer
      12th Congress IXA (International Xenotransplantation Association 2013).
    • Place of Presentation
      Osaka
    • Related Report
      2013 Annual Research Report
  • [Presentation] GalT-KO ブタ肺による急性期グラフト機能不全抑制効果の体外循環肺移植モデルによる評価2012

    • Author(s)
      佐原寿史, 清水 章, 関島光裕, 田崎正行, 瀬戸山健太郎, 長嶋比呂志, 伊達洋至, 山田和彦
    • Organizer
      第29回日本呼吸器外科学会総会
    • Place of Presentation
      秋田市
    • Related Report
      2013 Final Research Report
  • [Presentation] ワークショップ【臓器移植に対する先端研究-次世代の実現を目指す戦略-】臓器特異性に基づく新たな異種免疫反応制御戦略-前臨床ブタ・サル移植モデルによる検討2012

    • Author(s)
      佐原寿史
    • Organizer
      第48回日本移植学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
  • [Presentation] Protective effect of anti-high-mobility group box-1 (HMGB1) antibody on pulmonary ischemia-reperfusion injury in miniature swine.2012

    • Author(s)
      Sahara H, Shimizu A, Sekijima M, Setoyama K, Oku M, Nishimura H, Yamada K
    • Organizer
      International Society for Heart and Lung Transplantation 32nd Annual Meeting
    • Place of Presentation
      Prague
    • Related Report
      2012 Annual Research Report
  • [Presentation] Donor preconditioning with carbon monoxide (CO) prolongs lung graft survival in miniature swine.2012

    • Author(s)
      Sahara H, Shimizu A, Tasaki M, Sekijima M, Oku M, Nishimura H, Iwamoto E, Setoyama K, Yamada K
    • Organizer
      International Society for Heart and Lung Transplantation 32nd Annual Meeting
    • Place of Presentation
      Prague
    • Related Report
      2012 Annual Research Report
  • [Presentation] High-Mobility Group Box-1 as a novel therapeutic target for reducing pulmonary ischemia-reperfusion injury in CLAWN miniature swine.2012

    • Author(s)
      Sahara H, Shimizu A, Sekijima M, Setoyama K, Oku M, Nishimura H, Yamada K
    • Organizer
      24th International Congress of the Transplantation Society
    • Place of Presentation
      Berlin
    • Related Report
      2012 Annual Research Report
  • [Presentation] Attenuation of hyperacute dysfunction and coagulopathy in GalT-KO pulmonary xenotransplantation.2012

    • Author(s)
      Sahara H, Nagashima H, Sekijima M, Tasaki M, Setoyama K, Matsunari H, Nakano K, Date H, Shimizu A, Yamada K
    • Organizer
      24th International Congress of the Transplantation Society
    • Place of Presentation
      Berlin
    • Related Report
      2012 Annual Research Report
  • [Presentation] Carbon monoxide administered only to the donor is sufficient to prolong pulmonary allograft survival across a fully MHC-mismatched barrier in CLAWN miniature swine.2012

    • Author(s)
      Sahara H, Sekijima M, Tasaki M, Oku M, Nishimura H, Iwanaga T, Iwanaga T, Sekijima A, Setoyama K, Shimizu A, Yamada K
    • Organizer
      24th International Congress of the Transplantation Society
    • Place of Presentation
      Berlin
    • Related Report
      2012 Annual Research Report
  • [Presentation] GalT-KOブタ肺による急性期グラフト機能不全抑制効果の体外循環肺移植モデルによる評価2012

    • Author(s)
      佐原寿史
    • Organizer
      第29回日本呼吸器外科学会総会
    • Place of Presentation
      秋田
    • Related Report
      2012 Annual Research Report
  • [Presentation] Prevention of hyper-acute pulmonary xenograft dysfunction using GalT-KO swine in an ex-vivo lung perfusion model2011

    • Author(s)
      Sahara H, Nagashima H, Sekijima M, Tasaki M, Setoyama K, Matsunari H, Nakano K, Date H, Shimizu A, Yamada K
    • Organizer
      CTS (Cell Transplant Society)-IXA (International Xenotransplantation Association) 2011 Joint Congress
    • Place of Presentation
      マイアミビーチ
    • Year and Date
      2011-10-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 体外循環回路を用いたEx-vivo GalT-KOブタ肺移植モデルによる急性期グラフト機能不全抑制効果の評価2011

    • Author(s)
      佐原寿史、清水章、関島光裕.田崎正行、瀬戸山健太郎.長嶋比呂志、伊達洋至、山田和彦
    • Organizer
      第64回日本胸部外科学会定期学術集会
    • Place of Presentation
      名古屋市
    • Year and Date
      2011-10-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] シンポジウム2.次世代の移植医療に向けて:先端技術を応用した移植医療の開発「臨床応用を目指したブタ・サル間異種移植実験」2011

    • Author(s)
      佐原寿史、長嶋比呂志、齋藤敏樹、島津美樹、伊達洋至、清水章、山田和彦
    • Organizer
      第47回日本移植学会総会
    • Place of Presentation
      仙台市
    • Year and Date
      2011-10-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] Prevention of hyper-acute pulmonary xenograft dysfunction using GalT-KO swine in an ex-vivo lung perfusion model2011

    • Author(s)
      Sahara H, Nagashima H, Sekijima M, Tasaki M, Setoyama K, Matsunari H, Nakano K, Date H, Shimizu A, Yamada K
    • Organizer
      CTS (Cell Transplant Society) -IXA (International Xenotransplantation Association) 2011 Joint Congress
    • Place of Presentation
      Miami beach, FL, US
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム2.次世代の移植医療に向けて : 先端技術を応用した移植医療の開発「臨床応用を目指したブタ・サル間異種移植実験」2011

    • Author(s)
      佐原寿史, 長嶋比呂志, 齋藤敏樹, 島津美樹, 伊達洋至, 清水 章, 山田和彦
    • Organizer
      第47回日本移植学会総会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Final Research Report
  • [Presentation] Recent progress in major research laboratories in East Asia - Preclinical study - “Preclinical large animal xenotransplantation projects in Kagoshima”

    • Author(s)
      Sahara H, Yamada K
    • Organizer
      The 2nd Symposium of the East Asia Xenotransplantation Association
    • Place of Presentation
      Osaka
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~xenotx/

    • Related Report
      2013 Final Research Report
  • [Remarks] 鹿児島大学医用ミニブタ・先端医療開発研究センターホームページ

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~xenotx/index.html

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi