Reduction of donor mononuclear phagocytes during ex vivo lung perfusion attenuates ischemia-reperfusion injury in a rat lung transplantation model

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09302
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Kyoto University
• Principal Investigator: Ohshumi Akihiro 京都大学, 医学研究科, 助教 (90829574)
• Co-Investigator(Kenkyū-buntansha): 芳川 豊史 名古屋大学, 医学系研究科, 教授 (00452334) ; 伊達 洋至 京都大学, 医学研究科, 教授 (60252962)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肺移植 / 体外肺灌流 / 虚血再灌流傷害 / 単核貪食細胞

Outline of Final Research Achievements

Despite flushing with preservation solution during donor procurement, donor lungs still contain leukocytes. Among leukocyte subtypes, mononuclear phagocytes are considered the main cause of lung injury. Ex vivo lung perfusion (EVLP) has been applied for the pretransplant assessment of lung quality. The true potential of EVLP lies not only in evaluating the quality of donor grafts but also in reconditioning them.
In this study, clodronate-liposome was administered into the perfusate during EVLP in a rat model and mononuclear phagocytes in donor lungs were significantly reduced using this drug. Moreover, lung injury after lung transplantation was significantly attenuated in the treatment group compared with the control group.

Free Research Field

肺移植

Academic Significance and Societal Importance of the Research Achievements

肺移植においてドナー肺不足は深刻な問題である。前述のように、ドナー肺内には白血球が残存し、特に白血球分画の中で単核貪食細胞は移植後のドナー肺の機能不全に大きく関与するとされている。貴重な使用し得るドナー肺を増加させ、かつ移植肺の機能を向上させるには、移植前に治療を行い、かつ機能評価を行うことが極めて重要である。本小動物研究においては、体外肺灌流中に薬剤を用いて単核貪食細胞を除去し、移植後の肺傷害を軽減することを見出した。今後、中・大動物においても効果を確認する必要はあるが、同治療法は、移植前の治療・評価により、移植し得るドナー肺を増加させ、かつ質を改善させうる、非常に有用な手段と考える。