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Reducing ischemic lung perfusion injury by artificial hemoglobin

Research Project

Project/Area Number 16K10686
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory surgery
Research InstitutionNagasaki University

Principal Investigator

MIYAZAKI Takuro  長崎大学, 病院(医学系), 助教 (00584749)

Co-Investigator(Kenkyū-buntansha) 土谷 智史  長崎大学, 医歯薬学総合研究科(医学系), 准教授 (30437884)
永安 武  長崎大学, 医歯薬学総合研究科(医学系), 教授 (80284686)
畑地 豪  長崎大学, 病院(医学系), 助教 (80437889)
酒井 宏水  奈良県立医科大学, 医学部, 教授 (70318830)
Research Collaborator SAKAI Hiromi  
TAKAGI Katsunori  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords人工赤血球 / 臓器保存 / 肺移植 / 呼吸器外科学 / 虚血再還流 / 臓器保護 / 外科 / 虚血再灌流生涯
Outline of Final Research Achievements

Ischemic reperfusion injury (IRI) still has been a big problem to be solved for long term survival for lung transplant recipients. Hemoglobin vesicles (HbVs) are artificial oxygen carriers that encapsulate purified human Hb solution in phospholipid vesicles. The smaller average particle size of HbVs, compared to human red blood cells, allows better perfusion through narrow capillaries. The purpose of this study was to evaluate the effect of HbVs with lung preservation solutions to improve IRI.
In our rat model, we could not identify the usefulness of HbVs with lung preservation. Current lung preservation solution is strong enough not to be needed HbVs. Thus we used HbVs for evaluation of decellularization ex-vivo perfusion models. Recellularization of decellularized organ scaffold is a promising option for organ regeneration. In rat model, we demonstrated that HbVs was the good evaluation tool for ex vivo functional analysis as HbVs -PBS solution passed through regenerated lungs.

Academic Significance and Societal Importance of the Research Achievements

人工赤血球(Hb)が小粒子径で高い酸素運搬能力がある事に注目し、肺移植で重篤な合併症である移植肺の虚血還流障害(IRI)を防止・抑制するかを小動物モデルで検討した。
IRIの程度にHb投与の差は認められず、現在の保存液はHbの効果を必要とする程障害されない事を示唆した。研究過程で肺の酸素化能を測定できる試験薬としての能力に着眼し、再生肺モデルで再生肺の酸素化能力が測定可能かを検討し、アポトーシスが抑制されることを証明した。この結果は人工赤血球を用いた新灌流システムが肺保護に繋がる第一歩と考えた。ラット摘出肺、再生肺ともに換気でHb溶液は酸素化され肺拡散能をex vivoで検査するモデルとなる。

Report

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

    (2 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (1 results)

  • [Journal Article] Sodium hydroxide based non-detergent decellularizing solution for rat lung2018

    • Author(s)
      Sengyoku H, Tsuchiya T, Obata T, Doi R, Hashimoto Y, Ishii M, Sakai H, Matsuo N, Taniguchi D, Suematsu T, Lawn M, Matsumoto K, Miyazaki T, Nagayasu T
    • Journal Title

      Organogenesis

      Volume: 14 Pages: 94-106

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 細胞置換技術を利用した肺再生 -細胞外マトリックスに関わる研究2019

    • Author(s)
      土谷 智史、松本 桂太郎、宮崎 拓郎、畑地 豪、土肥 良一郎、渡邉 洋之助、谷口 大輔、永安 武
    • Organizer
      第36回呼吸器外科学会学術集会
    • Related Report
      2018 Annual Research Report

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

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