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2013 Fiscal Year Final Research Report

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

Research Project

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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
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
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.

  • Research Products

    (10 results)

All 2014 2013 2012 2011 Other

All Journal Article (3 results) (of which Peer Reviewed: 2 results) Presentation (6 results) Remarks (1 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) Pages: 157-64

    • DOI

      10.1111/xen.12031

    • Peer Reviewed
  • [Journal Article] Current progress in xenogeneic tolerance2012

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

      Curr Opin Organ Transplant

      Volume: 17(2) Pages: 168-73

    • DOI

      10.1097/MOT.0b013e32835090f6

    • 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

  • [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
    • Year and Date
      20140529-30
  • [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
    • Year and Date
      20131110-13
  • [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
    • Year and Date
      20130903-06
  • [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
    • Year and Date
      20120517-18
  • [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
    • Year and Date
      20111023-26
  • [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
      20111004-06
  • [Remarks]

    • URL

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

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Published: 2015-06-25  

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