Research aiming to achieve both inflammation suppression and tissue regeneration using secreted peptides derived from mesenchymal stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K10014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57040:Regenerative dentistry and dental engineering-related
• Research Institution: Iwate Medical University
• Principal Investigator: Chosa Naoyuki 岩手医科大学, 歯学部, 准教授 (80326694)
• Co-Investigator(Kenkyū-buntansha): 下山 佑 岩手医科大学, 歯学部, 准教授 (90453331)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 間葉系幹細胞 / 炎症抑制 / 組織再生

Outline of Final Research Achievements

Mesenchymal stem cells (MSCs) play an important role in tissue regeneration. In this study, we investigated the effects of TGF-β secreted from MSCs and macrophages accumulated in inflamed tissues on tissue regeneration. MSCs stimulated by TGF-β had increased expression levels of both NGF and IL-6. NGF secreted by the MSCs induced neurite outgrowth, and neurite outgrowth was enhanced by IL-6, which was also secreted. On the other hand, TGF-β induced extracellular matrix mineralization during osteogenic differentiation of MSCs. This mineralization was significantly enhanced in the presence of CTGF. Therefore, it was suggested that CTGF promotes osteogenic differentiation of MSCs.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

近年、間葉系幹細胞（MSC）が組織再生以外にも、免疫抑制作用などの生命維持のために重要な役割を担っていることが注目されている。本研究では、炎症の場に集積したMSCや炎症関連細胞から分泌されたサイトカインが炎症抑制やそれに引き続く組織再生におよぼす影響を検討した。その結果、MSCから分泌されるSCRG1の炎症抑制作用に加え、MSCやマクロファージから分泌されるTGF-βの組織再生能を明らかにした。本研究の成果はペプチド製剤の開発や、免疫担当細胞とMSCの相互作用を解明、さらには歯周炎や慢性関節リウマチなど炎症性骨吸収や組織破壊を伴った疾患の治療法確立にも寄与するものである。