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

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10503
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Asahikawa Medical College
• Principal Investigator: Matsuno Naoto 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: 肝臓保存 / 機械灌流保存 / 人工赤血球 / 移植臓器保存液 / 心停止ドナー肝

Outline of Final Research Achievements

Pig livers were excised after 60 minutes of warm ischemic time and were preserved under one of three preservation conditions for 4 hours. The preservation conditions were as follows: cold storage (CS group; N = 5), Hypothermic machine preservation (HMP) (HMP group; N = 5), subnormothermic MP (21゜C) ; N = 5) SNMP with HbVs (SNMP+HbV group; N = 5). Autologous blood perfusion was performed for 2 hours in an isolated liver reperfusion model). The oxygen consumption of the SNMP and SNMP +HbV group was higher than the HMP groups (p < 0.05). During the reperfusion, AST level in the SNMP+HbV group was lower than that in the CS, HMP and SNMP groups. The changes in pH was significantly lower in SNMP+HbV group. The ultrastructural findings indicated that the mitochondria of the SNMP+HbV group was well maintained. The SNMP +HbVs preservation solution protected against metabolic acidosis and preserved the liver function after reperfusion injury in the DCD liver.

Free Research Field

肝臓外科、移植外科、臓器保存

Academic Significance and Societal Importance of the Research Achievements

研究成果は、ブタを用いた前臨床的研究であること、灌流保存技液による臓器機能回復をめざした点で我が国初の画期的研究成果だと考えている。臓器移植手術では、移植直前に臓器内血球成分を洗い流すため、人工赤血球が体内に入ることはなく、臨床応用のハードルは高くないと考えている。今回、虚血再灌流障害を抑制することに成功した。心停止肝臓のみならず、小児医療などで期待の高い分割肝あるいは脂肪肝など適用に課題のある臓器移植を可能とする可能性がある。赤血球循環技術はdrug delivery systemや臓器培養、再生医療との共創により次世代型治療との複合による新しい時代の研究を切り開くプラットフォームになる