Establishment of a Preservation Method for Mesenchymal Stem Cell-Derived Extracellular Vesicles and Development of a Novel Treatment for Acute Liver Failure

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07998
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Yamagata University
• Principal Investigator: Haga Hiroaki 山形大学, 医学部, 准教授 (70466613)
• Co-Investigator(Kenkyū-buntansha): 星川 恭子 山形大学, 医学部, 助教 (20613053) ; 勝見 智大 山形大学, 医学部, 助教 (70637355)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 細胞外小胞 / 間葉系幹細胞 / 急性肝不全 / Extracellular Vesicles

Outline of Final Research Achievements

In mice with acute liver failure, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been shown to improve liver function and liver tissue. However, in urgent clinical settings, it is necessary to establish an effective preservation method for MSC-EVs. We investigated the lyophilization method for preserving MSC-EVs and studied the effects of lyophilized MSC-EVs on mice with acute liver failure. By comparing lyophilization methods using PBS, 1% sucrose solution, and 5% sucrose solution, it was demonstrated that the number, RNA, and morphology of MSC-EVs were best maintained with the 5% sucrose solution. Furthermore, lyophilized MSC-EVs in 5% sucrose solution were confirmed to improve liver function and liver tissue in mice with acute liver failure, similarly to non-lyophilized MSC-EVs.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

昏睡型急性肝不全は、死亡率が極めて高い疾患であり、肝臓移植を要する患者も存在する。しかし、深刻なドナー不足のため、新しい肝再生医療の開発が必要とされる。急性肝不全マウスにおいて、MSC-EVは肝機能改善に寄与するが、臨床応用を考えた際に問題となるのはMSC-EVの保存方法である。間葉系幹細胞の培養液からMSC-EVを抽出するには時間がかかるため、緊急性を有する臨床においてはMSC-EVの有効な保存方法の確立が必要である。今回、我々はMSC-EVの凍結乾燥法の確立と、その凍結乾燥MSC-EVが急性肝不全マウスの改善に寄与することを示した。これにより、EVの臨床応用に一歩近づくものと考えられる。