Amelioration of rejection after lung transplant by newly developed gas carrier.

• Project/Area Number: 17K10800
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Jikei University School of Medicine (2018-2019); Keio University (2017)
• Principal Investigator: Ohtsuka Takashi 東京慈恵会医科大学, 医学部, 教授 (40306717)
• Co-Investigator(Kenkyū-buntansha): 下田 将之 慶應義塾大学, 医学部(信濃町), 准教授 (70383734)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肺移植 / 拒絶反応 / Ｔ細胞 / 制御性Ｔ細胞 / 移植

Outline of Final Research Achievements

We evaluated the expression of matrix metalloproteinase (MMP) 9 and 13 in mouse trachea transplant model. We showed that MMP-9 and MMP-13 m-RNA were increased in allograft compared with in those of isograft. We also found that protein of MMP-9 and MMP-13 were increased in allograft compared with in those of isograft. We administered carbon monoxide by new gas carrier and showed that MMP-9 and MMP-13 mRNA were decreased in allograft compared with those in allograft treated with control vesicle. The rejection was ameliorated in the allograft treated with carbon monoxide compared with the allograft treated with control vesicle.

Academic Significance and Societal Importance of the Research Achievements

一酸化炭素投与により、肺移植後拒絶反応が抑制されることを示した。また一酸化炭素投与により、MMP-9、MMP-13の発現もコントロールされることが分かった。ガス運搬体により一酸化炭素を生体に投与可能な事も分かった。今後は他の臓器でもガス運搬体による一酸化炭素投与が可能で、移植拒絶反応の抑制が可能であれば移植後の拒絶反応の治療に貢献出来る可能性がある。

Research Products

• [Journal Article] Infiltration of tumor‐associated macrophages is involved in tumor programmed death‐ligand 1 expression in early lung adenocarcinoma (2020)
  • Author(s): Shima Toshiyuki、Shimoda Masayuki、Shigenobu Takao、Ohtsuka Takashi、Nishimura Tomoyasu、Emoto Katsura、Hayashi Yuichiro、Iwasaki Tatsuro、Abe Takayuki、Asamura Hisao、Kanai Yae
  • Journal Title: Cancer Science Volume: 111 Issue: 2 Pages: 727-738
  • DOI: 10.1111/cas.14272
  • Peer Reviewed / Open Access
• [Journal Article] The prevention of tracheal graft occlusion using pioglitazone: A mouse tracheal transplant model study. (2019)
  • Author(s): Shigenobu T, Ohtsuka T ,Shimoda M
  • Journal Title: Transplant Immunology Volume: 53 Pages: 21-27
  • DOI: 10.1016/j.trim.2018.12.002
  • Peer Reviewed
• [Presentation] Pioglitazone induces infiltrations of regulatory T cells in the tracheal graft and attenuates allograft rejection. (2019)
  • Author(s): Takashi Ohtsuka
  • Organizer: 39th annual meeting of International society of heart and lung transplantation
  • Int'l Joint Research
• [Presentation] Peroxisome proliferator-activated receptor（PPAR）-γアゴニストによるマウス気管移植での拒絶反応抑制 (2019)
  • Author(s): 大塚 崇
  • Organizer: 第119回 日本外科学会定期学術集会
• [Presentation] Peroxisome proliferator-activated receptor（PPAR）-γアゴニストによるマウス気管移植での拒絶反応抑制 (2019)
  • Author(s): 大塚 崇
  • Organizer: 第119回日本外科学会定期学術集会
• [Presentation] Pioglitazone Induces Infiltrations of Regulatory T Cells in the Tracheal Graft and Attenuates Allograft Rejection (2019)
  • Author(s): Takashi Ohtsuka
  • Organizer: International society for heart and lung transplantation
  • Int'l Joint Research