Application of artificial oxygen-carrying hemoglobin vesicles for marginal liver grafts in machine perfusion preservation

2019 Fiscal Year Annual Research Report

• Project/Area Number: 17K10503
• Research Institution: Asahikawa Medical College
• Principal Investigator: 松野 直徒 旭川医科大学, 医学部, 特任教授 (00231598)
• Co-Investigator(Kenkyū-buntansha): 酒井 宏水 奈良県立医科大学, 医学部, 教授 (70318830) ; 小原 弘道 首都大学東京, システムデザイン研究科, 准教授 (80305424)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 人工赤血球 / 臓器灌流保存 / 心肺停止ドナー / 虚血再灌流障害

Outline of Annual Research Achievements

ブタ心肺停止肝臓を用い、酸素化灌流保存ののちEx Vivo再灌流モデルで評価した。灌流保存液に人工赤血球を含有させ濃度別に効果判定をした。また虚血再灌流モデルには自己血液を用い評価項目を圧、抵抗、肝機能、血液ガス分析などで評価する事を確立した。人口赤血球含有臓器灌流保存液は現行のUW液を用いた単純冷却法よりも有意に酸素消費量の増加、肝細胞臓機能（AST,LDH)の低下、組織中TNFαの低下を認めた。電顕所見においてもミトコンドリア小胞体の膨化を抑制をした。
この研究成果には下記の如く論文として発表した。
Tatsuya Shonaka et al: Impact of human-derived hemoglobin based oxygen vesicles as a machine perfusion solution for liver donation after cardiac death in a pig model, PLOS ONE, December 11, 2019, DOI: 10.1371/journal.pone.0226183, PMID: 31825976

Research Products

• [Journal Article] Initial perfusate purification during subnormothermic machine perfusion for porcine liver donated after cardiac death (2020)
  • Author(s): Hiromichi Obara, Noriyuki Morito, Naoto Matsuno, Ryo Yoshikawa, Tetsuya Nakajo, Mikako Gochi, Masahide Otani, Tatsuya Shonaka, Hiroyuki Furukawa
  • Journal Title: Journal of Artificial Organs Volume: 23 Pages: 62～69
  • DOI: https://doi.org/10.1007/s10047-019-01123-5
  • Peer Reviewed
• [Journal Article] Impact of Machine Perfusion on Sinusoid Microcirculation of Liver Graft Donated After Cardiac Death (2020)
  • Author(s): Kanazawa Hiroyuki、Obara Hiromichi、Yoshikawa Ryo、Meng Lingtong、Hirano Toshihiko、Okada Yoko、Nishikawa Yuji、Matsuno Naoto
  • Journal Title: Journal of Surgical Research Volume: 245 Pages: 410～419
  • DOI: https://doi.org/10.1016/j.jss.2019.07.058
  • Peer Reviewed
• [Journal Article] Applicability of Hypothermic Oxygenate Machine Perfusion Preservation for Split-Liver Transplantation in a Porcine Model: An Experimental Study (2020)
  • Author(s): Ishii Daisuke、Matsuno Naoto、Gochi Mikako、Otani Masahide、Shonaka Tatsuya、Takahashi Hiroyuki、Nishikawa Yuji、Yoshikawa Ryo、Obara Hiromichi、Miyamoto Kazutoshi、Furukawa Hiroyuki
  • Journal Title: Annals of Transplantation Volume: 25 Pages: 1～8
  • DOI: https://doi.org/10.12659/aot.919920
  • Peer Reviewed
• [Journal Article] 免疫抑制剤と臓器保存 Current topics of immunosuppression and preservation for organ transplantation (2020)
  • Author(s): 松野直徒、庄中達也、高橋裕之、萩原正弘、今井浩二、横尾英樹、合地美香子、大谷将秀、古川博之、石井大介、小原弘道
  • Journal Title: 日中医学 Volume: Vol.35 No.1 Pages: 2～7
• [Journal Article] Impact of human-derived hemoglobin based oxygen vesicles as a machine perfusion solution for liver donation after cardiac death in a pig model (2019)
  • Author(s): Shonaka Tatsuya、Matsuno Naoto、Obara Hiromichi、Yoshikawa Ryo、Nishikawa Yuji、Ishihara Yo、Bochimoto Hiroki、Gochi Mikako、Otani Masahide、Kanazawa Hiroyuki、Azuma Hiroshi、Sakai Hiromi、Furukawa Hiroyuki
  • Journal Title: PLOS ONE Volume: 14 Pages: 1～17
  • DOI: https://doi.org/10.1371/journal.pone.0226183
  • Peer Reviewed
• [Journal Article] 機械灌流による代謝に着目した移植のための臓器機能評価技術、 Organ viability assessment technology using machine perfusion for transplantation. (2019)
  • Author(s): 小原弘道、吉川 遼、松野直徒、中條哲也、絵野沢 伸、平野俊彦
  • Journal Title: Organ Biology 2019 Volume: Vol26 No2 Pages: 123～128
• [Presentation] Present status of transplant organ preservation by dynamic machine perfusion system: How important is the development of a novel organ preservation solution? (2019)
  • Author(s): Naoto Matsuno
  • Organizer: 第26回日本血液代替物学会年次大会 同時開催 第17回血液代替物国際会議―The 17th International Symposium on Blood Substitutes and Oxygen Therapeutics(ⅩⅤⅡ-ISBS-2019)(奈良県)
  • Int'l Joint Research / Invited
• [Presentation] The efficacy of hemoglobin vesicles(HbV)containing solution in machine perfusion in donation after cardiac death(DCD) in pig liver model (2019)
  • Author(s): Tatsuya Shonaka、Naoto Matsuno、Hiromichi Obara、Ryo Yoshikawa、Yuji Nishikawa、Yo Ishihara、Hiroki Bochimoto、Mikako Gochi、Masahide Otani、Hiroyuki Kanazawa、Hiroshi Azuma、Hiromi Sakai、Hiroyuki Furukawa
  • Organizer: 第26回日本血液代替物学会年次大会 同時開催 第17回血液代替物国際会議―The 17th International Symposium on Blood Substitutes and Oxygen Therapeutics(ⅩⅤⅡ-ISBS-2019)(奈良県)
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] CONNECTOR AND FLUID SUPPLY SYSTEM (2019)
  • Inventor(s): M Matsumura, N Matsuno et al.
  • Industrial Property Rights Holder: M Matsumura, N Matsuno et al.
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: WO2018180544
  • Overseas