2021 Fiscal Year Final Research Report

Development of rejection control method by mesenchymal stem cells using original rat lung transplantation model

Research Project

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Project/Area Number	19K09309
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55040:Respiratory surgery-related
Research Institution	Nagasaki University
Principal Investigator	MIYAZAKI TAKURO 長崎大学, 病院(医学系), 講師 (00584749)
Co-Investigator(Kenkyū-buntansha)	土肥良一郎長崎大学, 病院(医学系), 助教 (00817786) 土谷智史長崎大学, 医歯薬学総合研究科(医学系), 准教授 (30437884) 渡邉洋之助長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (30457551) 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)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	呼吸器外科学 / 脂肪肝細胞 / 拒絶反応
Outline of Final Research Achievements	We have focused on the immunosuppressive effects of mesenchymal stem cells (MSCs). MSCs have shown sustained immunosuppressive effects in the liver and other organs, and reductions in the dose of immunosuppressive agents and a state of immunological tolerance have also been established. However, in the area of lung transplantation (LTx), the study has lagged behind. If an effective stem cell therapy is established, it will reduce rejection and increase the survival rate after LTx, and reduce long-term side effects caused by immunosuppressive agents. To find the optimal stem cell source for stem cell therapy, we compared the immunosuppressive effects of recipient-derived adipose stem cells, donor-derived adipose stem cells, and adipose stem cells from other departments, and found no obvious significant difference, but recipient-derived stem cells, which showed a tendency to reduce rejection more However, recipient-derived adipose stem cells showed more immunosuppressive effect.
Free Research Field	呼吸器外科学
Academic Significance and Societal Importance of the Research Achievements	今回の研究によって、肺移植においては脂肪由来間葉系幹細胞の投与タイミングは移植直後の方が拒絶反応を軽減することが判明した。肺移植において間葉系幹細胞の投与タイミングの違いによる免疫抑制効果および拒絶反応の減弱効果を直接的に比較検討した研究は存在せず、臓器移植に間葉系幹細胞の免疫抑制効果を応用するにあたり重要な情報となる。臓器移植後の拒絶反応に対して間葉系幹細胞を使用し、肺移植後の予後の改善が期待できると共に、従来の免疫抑制剤の減量も可能であり、免疫抑制剤の有害事象を軽減することも期待される。結果的にレシピエントのQOLの改善、医療経済的に多大な利益をもたらす可能性がある。