2023 Fiscal Year Final Research Report

A Study on Signal Transductions of MSC Culture in Total Autologous Angiogenic Therapy

Research Project

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Project/Area Number	20K09133
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55030:Cardiovascular surgery-related
Research Institution	Tokyo Medical University
Principal Investigator	Fukuda Shoji 東京医科大学, 医学部, 教授 (70362069)
Co-Investigator(Kenkyū-buntansha)	落谷孝広東京医科大学, 医学部, 特任教授 (60192530)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	エクソソーム / 閉塞性動脈硬化症 / 重症下肢虚血 / 創薬 / 下肢切断
Outline of Final Research Achievements	1. Normal human cell lines (bone marrow mesenchymal stem cells (MSCs)) that are commercially available were used to identify angiogenesis-related microRNAs. (2020) 2. Using MSCs as in the previous step, the effects of the identified angiogenesis-related microRNAs were evaluated in vitro (Matrigel). We also evaluated the angiogenic effects of exosomes containing the microRNAs. (2021) 3. Lentiviral vectors were transfected into MSCs to intentionally induce strong expression of the identified microRNAs. Exosomes were obtained from the supernatant of the culture. The exosomes were isolated from the culture supernatant, and the resulting angiogenesis-related exosome-strongly expressing solution was positioned as an angiogenic agent, and its effects were evaluated in vitro. (2022-2023)
Free Research Field	心臓血管外科
Academic Significance and Societal Importance of the Research Achievements	閉塞性動脈硬化症の最重症例である重症下肢虚血に対する治療では、期待通りの結果が出ていない現状がある。この疾患で年間1万人が下肢切断となている。私たちが実施している完全自家血管新生療法は、まだ症例数は少ないが、主要評価項目の治療１年後切断回避生存率が６７％で、歴史的データでの４５％と比較すると今後の結果に期待が寄せられる。しかし、同療法は患者間に治療効果の差がみられ、その差の原因が血管新生タンパクではなく、ある種のマイクロRNAあるいはエクソソームによるものの可能性が明らかになった。本研究により下肢切断回避に関するエクソソーム創薬の可能性が示唆された。