Protective effects of hepatocyte growth factor during ex vivo lung perfusion on ischemia-reperfusion injury in lung transplantation

• Project/Area Number: 18K16416
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Kyoto University
• Principal Investigator: Nakajima Daisuke 京都大学, 医学研究科, 講師 (50812286)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 体外肺灌流保存 / EVLP / 肺移植 / 心停止ドナー / 肝細胞増殖因子 / HGF / 虚血再灌流障害 / Ex vivo lung perfusion

Outline of Final Research Achievements

There has been a progressive increase in the number of patients on the waiting list, which continually exceeds the number of available organs in Japan. The use of donation after circulatory death (DCD) donors can resolve this problem. We simulated a clinically relevant uncontrolled DCD model in the current study. Ex vivo lung perfusion (EVLP) recreated the physiological environment by maintaining normothermia and providing the essential substrates for cellular metabolism, which enabled organ viability assessment of DCD donor lungs.

Academic Significance and Societal Importance of the Research Achievements

心停止ドナー肺は、心停止に至る過程や心停止後の温虚血、冷虚血などにより様々な障害を受けている可能性がある。動物モデルで機能評価として確立した体外肺灌流保存（EVLP）システムを、心停止ドナー肺の各障害の治療・修復のプラットフォームとして用いることができる。すなわちEVLP中に肝細胞増殖因子などの修復因子を投入することにより、障害を受けたドナー肺を移植できる状態に改善させることで、今後の肺移植におけるドナーソースの拡大に期待される。

Research Products

• [Journal Article] Successful lung transplant cases with ex vivo lung perfusion assessment of extended criteria donor lungs (2022)
  • Author(s): Daisuke Nakajima, Shunichi Nagata,Hidenao Kayawake, Satona Tanaka, Yoshito Yamada, Yojiro Yutaka, Akihiro Ohsumi, Masatsugu Hamaji, Toyofumi F. Chen-Yoshikawa, Hiroshi Date
  • Journal Title: General Thoracic and Cardiovascular Surgery Volume: 70 Issue: 4 Pages: 406-412
  • DOI: 10.1007/s11748-022-01774-x
  • Peer Reviewed
• [Journal Article] Ex vivo lung perfusion in lung transplantation (2021)
  • Author(s): Nakajima Daisuke、Date Hiroshi
  • Journal Title: General Thoracic and Cardiovascular Surgery Volume: 69 Issue: 4 Pages: 625-630
  • DOI: 10.1007/s11748-021-01609-1
  • Peer Reviewed
• [Journal Article] Living-donor lobar lung transplants provide comparable pulmonary function to cadaveric lung transplants (2020)
  • Author(s): Nakajima D, Chen-Yoshikawa TF, Ohsumi A, Date H
  • Journal Title: Journal of Thoracic and Cardiovascular Surgery Volume: 159 Issue: 3 Pages: 734-738
  • DOI: 10.1016/j.jos.2019.08.002
  • Peer Reviewed
• [Journal Article] Gastrointestinal complications after lung transplantation in Japanese patients. (2018)
  • Author(s): Kayawake H, Chne-yoshikawa TF, Motoyama H, Hamaji M, Nakajima D, Aoyama A, Date H.
  • Journal Title: Surg Today Volume: -
  • Peer Reviewed / Open Access
• [Presentation] 肺移植におけるEx Vivo Lung Perfusionの現状 (2021)
  • Author(s): 中島大輔、芳川豊史、伊達洋至
  • Organizer: 第57回日本移植学会総会
• [Presentation] Ex vivo lung perfusion（EVLP）導入によるマージナルドナー肺の使用拡大 (2021)
  • Author(s): 中島大輔、田中里奈、山田義人、豊洋次郎、大角明宏、濱路政嗣、芳川豊史、伊達洋至
  • Organizer: 第38回日本呼吸器外科学会学術集会
• [Presentation] 本邦の肺移植におけるEx Vivo Lung Perfusionの臨床導入の現況 (2020)
  • Author(s): 中島大輔、芳川豊史、伊達洋至
  • Organizer: 第73回日本胸部外科学会定期学術集会
• [Presentation] Ex vivo lung perfusionを用いたマージナルドナー肺の移植前治療 (2020)
  • Author(s): 中島大輔、芳川豊史、伊達洋至、Shaf Keshavjee
  • Organizer: 第56回日本移植学会総会
• [Presentation] 肺移植における体外肺灌流保存（EVLP）を用いたマージナルドナー肺の治療 (2019)
  • Author(s): 中島大輔、芳川豊史、伊達洋至
  • Organizer: 第55回日本移植学会総会