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Development of the regulation of inflammation in the field of cardiovascular surgery using human iPS cell-derived mesenchymal stem cells

Research Project

Project/Area Number 16H05424
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cardiovascular surgery
Research InstitutionKyoto University

Principal Investigator

Yamazaki Kazuhiro  京都大学, 医学研究科, 講師 (50464227)

Co-Investigator(Kenkyū-buntansha) 升本 英利  国立研究開発法人理化学研究所, 生命機能科学研究センター, 上級研究員 (70645754)
南方 謙二  京都大学, 医学研究科, 講師 (60539675)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords心筋疾患外科学 / ヒトiPS細胞 / 間葉系幹細胞 / 循環器・高血圧 / 外科 / 移植・再生医療
Outline of Final Research Achievements

We established a protocol to efficiently stock human iPS cell-derived mesenchymal stem cells (MSC) by a freeze-thaw method. Next, we verified an attenuation of systemic inflammation and lung injury mediated by inflammatory cell infiltration by administrating MSCs in a rat cardiopulmonary bypass (CPB) model. Then we showed an increased effect of recombinant thrombomodulin for the attenuation of systemic inflammation and lung injury in a rat CPB model. Here we demonstrated a scientific basis for the establishment of a multidisciplinary therapeutic remedy of inflammation control in the field of cardiovascular surgery based on human iPS cell-derived MSCs.

Academic Significance and Societal Importance of the Research Achievements

心臓血管外科手術に関連する全身性炎症反応は致命的な合併症を引き起こしうる。間葉系幹細胞および化合物の併用による免疫寛容を利用した炎症反応制御は、これまでにない治療効果を期待しうることが本研究により示された。これらの成果は、今後増加が予想される心臓病患者に対する、より合併症の少ない外科治療を提供することに対する学術的基盤を提供しうるものであり、医療経済を含む社会的な意義が高いものと考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (22 results)

All 2018 2017 2016 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Int'l Joint Research: 4 results) Remarks (1 results)

  • [Journal Article] Sustained release of basic fibroblast growth factor using gelatin hydrogel improved left ventricular function through the alteration of collagen subtype in a rat chronic myocardial infarction model.2018

    • Author(s)
      Li Z, Masumoto H, Jo JI, Yamazaki K, Ikeda T, Tabata Y, Minatoya K.
    • Journal Title

      Gen Thorac Cardiovasc Surg.

      Volume: 66 Issue: 11 Pages: 641-647

    • DOI

      10.1007/s11748-018-0969-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A therapeutic angiogenesis of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel sheets in a canine chronic myocardial infarction model.2018

    • Author(s)
      Kumagai M, Minakata K, Masumoto H, Yamamoto M, Yonezawa A, Ikeda T, Uehara K, Yamazaki K, Ikeda T, Matsubara K, Yokode M, Shimizu A, Tabata Y, Sakata R, Minatoya K.
    • Journal Title

      Heart Vessels

      Volume: 33 Issue: 10 Pages: 1251-1257

    • DOI

      10.1007/s00380-018-1185-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Recovery Cardiopulmonary Bypass Model Without Transfusion or Inotropic Agents in Rats.2018

    • Author(s)
      Hirao S, Masumoto H, Itonaga T, Minatoya K.
    • Journal Title

      J Vis Exp

      Volume: ー Issue: 133 Pages: 133-133

    • DOI

      10.3791/56986

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic angiogenesis by local sustained release of microRNA-126 using poly lactic-co-glycolic acid nanoparticles in murine hindlimb ischemia.2017

    • Author(s)
      Tsumaru S, Masumoto H, Minakata K, Izuhara M, Yamazaki K, Ikeda T, Ono K, Sakata R, Minatoya K.
    • Journal Title

      J Vasc Surg.

      Volume: 印刷中 Issue: 4 Pages: 1209-1215

    • DOI

      10.1016/j.jvs.2017.08.097

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recombinant human soluble thrombomodulin prevents acute lung injury in a rat cardiopulmonary bypass model.2017

    • Author(s)
      Hirao S, Minakata K, Masumoto H, Yamazaki K, Ikeda T, Minatoya K, Sakata R.
    • Journal Title

      J Thorac Cardiovasc Surg.

      Volume: 154 Issue: 6 Pages: 1973-1983

    • DOI

      10.1016/j.jtcvs.2017.05.051

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fetal mesenchymal stem cells ameliorate acute lung injury in a rat cardiopulmonary bypass model.2017

    • Author(s)
      7.Taki T, Masumoto H, Funamoto M, Minakata K, Yamazaki K, Ikeda T, Sakata R.
    • Journal Title

      The Journal of Thoracic and Cardiovascular Surgery

      Volume: 153 Issue: 3 Pages: 726-734

    • DOI

      10.1016/j.jtcvs.2016.10.014

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 標準化と成績の向上を目指した自己弁温存大動脈基部置換術式の工夫.2018

    • Author(s)
      湊谷 謙司,山﨑 和裕,金光 ひでお,坂本 和久,井出 雄二郎,上田 遼馬,竹原 眞人,矢次 遥,植山 浩二,池田 義
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 心臓再生医療用のヒトiPS細胞由来心血管系細胞多層体の開発2018

    • Author(s)
      升本 英利,中根 武一郎,平尾 慎吾,瀧本 真也,李 子澎,金光 ひでお,植山 浩二,山﨑 和裕,池田 義,田畑 泰彦,山下 潤,湊谷 謙司
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大動脈弁輪拡張症に対する手術手技の工夫 2種類のバルサルバグラフトを用いたReimplantation法による自己弁温存基部再建術2018

    • Author(s)
      山﨑 和裕,上田 遼馬,竹原 眞人,坂本 和久,井出 雄二郎,金光 ひでお,南方 謙二,植山 浩二,池田 義,湊谷 謙司
    • Organizer
      第46回日本血管外科学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] BPA抵抗性のCTEPHに対しPEAを行い良好な結果を得た1症例2018

    • Author(s)
      山﨑 和裕,湊谷 謙司,竹原 眞人,上田 遼馬,工藤 雅文,坂本 和久,井出 雄二郎,植山 浩二,金光 ひでお,池田 義
    • Organizer
      第3回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 当科におけるRCA#3に対する冠動脈バイパス術の成績2018

    • Author(s)
      山﨑 和裕,金光 ひでお,坂本 和久,井出 雄二郎,工藤 雅文,竹原 眞人,上田 遼馬,植山 浩二,池田 義,湊谷 謙司
    • Organizer
      第23回日本冠動脈外科学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 右冠動脈#3に対するバイパス手術の成績2018

    • Author(s)
      山﨑 和裕,金光 ひでお,坂本 和久,工藤 雅文,境 次郎,中村 真、北方 悠太,山本 涼、井出 雄二郎,池田 義,湊谷 謙司
    • Organizer
      第71回日本胸部外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] MicroRNA-145封入ポリ乳酸グリコール酸共重合体ナノ粒子による静脈グラフト内膜肥厚抑制に関するウサギ頸動脈モデルを用いた検討2018

    • Author(s)
      西尾 博臣,升本 英利,川東 正英,坂本 和久,金光 ひでお,山﨑 和裕,池田 義,湊谷 謙司
    • Organizer
      第71回日本胸部外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] MicroRNA-145-loaded poly lactic-co-glycolic acid nanoparticles attenuate venous intimal hyperplasia in a rabbit vein graft disease model2018

    • Author(s)
      Nishio H, Masumoto H, Sakamoto K, Kanemitsu H, Ueyama K, Yamazaki K, Ikeda T, Minatoya K
    • Organizer
      第5回国際組織工学・再生医療学会世界会議
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 慢性B型解離に対する超低体温循環停止、SIRC(Straight incision with rib-cross)アプローチによる胸部下行、胸腹部大動脈置換術2017

    • Author(s)
      坂本 和久,山﨑 和裕,上田 遼馬,竹原 眞人,矢次 遥,中津 太郎,井出 雄二郎,升本 英利,金光 ひでお,植山 浩二,池田 義,湊谷 謙司
    • Organizer
      第70回日本胸部外科学会定期学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 胸腹部大動脈瘤人工血管置換術におけるCritical segmental arteryの確実な術中同定法2017

    • Author(s)
      山下 剛生,湊谷 謙司,山﨑 和裕,金光 ひでお,中津 太郎,坂本 和久,井出 雄二郎,植山 浩二,池田 義
    • Organizer
      第70回日本胸部外科学会定期学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 高度の心不全症状を有する機能性僧帽弁閉鎖不全症に対する手術成績の検討2017

    • Author(s)
      山﨑 和裕,南方 謙二,中津 太郎,坂本 和久,井出 雄二郎,升本 英利,金光 ひでお,植山 浩二,池田 義,湊谷 謙司,坂田 隆造.
    • Organizer
      第70回日本胸部外科学会定期学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Recombinant human soluble thrombomodulin prevents acute lung injury in a rat cardiopulmonary bypass model2016

    • Author(s)
      S. Hirao, K. Minakata, H. Masumoto, S. Setozaki, K. Yamazaki, T. Ikeda, R. Sakata
    • Organizer
      AHA Scientific session 2016
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ラット人工心肺モデルにおける遺伝子組換えトロンボモデュリン投与による急性肺障害抑制効果の検討2016

    • Author(s)
      平尾 慎吾,南方 謙二,升本 英利,船本 成輝,瀬戸﨑 修司,坂本 和久,中津 太郎,上原 京勲,山﨑 和裕,池田 義,坂田 隆造
    • Organizer
      第69回日本胸部外科学会定期学術集会
    • Place of Presentation
      岡山市
    • Year and Date
      2016-09-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Recombinant human soluble thrombomodulin prevents acute lung injury induced by cardiopulmonary bypass in rats2016

    • Author(s)
      S. Hirao, K. Minakata, H. Masumoto, S. Setozaki, K. Yamazaki, T. Ikeda, R. Sakata
    • Organizer
      European Society of Cardiology Congress
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2016-08-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Recombinant human soluble thrombomodulin prevents acute lung injury induced by cardiopulmonary bypass in a rat model2016

    • Author(s)
      Shingo Hirao, Kenji Minakata, Masaki Funamoto, Shuji Setozaki, Kazuhiro Yamazaki, Hidetoshi Masumoto, Tadashi Ikeda, and Ryuzo Sakata
    • Organizer
      24th Anual meeting of Asian Society for Cardiovascular and Thoracic Surgery
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2016-04-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 京都大学 心臓血管外科

    • URL

      http://kyoto-cvs.jp/

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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