Elucidation of the tissue regeneration initiation mechanism through MSCs and Macrophage interaction and development of tissue regeneration acceleration technology.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K23080
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Okayama University
• Principal Investigator: Tagashira Ryuji 岡山大学, 大学病院, 医員 (20882640)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: 間葉系幹細胞 / マクロファージ

Outline of Final Research Achievements

In a long bone injury model, it was suggested that the accumulation of M1 macrophages and mesenchymal stem cells (MSCs) in the damaged area, along with an increase in M2 macrophages, played an important role in tissue regeneration, as evidenced by delayed bone regeneration in the macrophage-depleted group through micro-CT analysis.

Co-culturing with MSCs resulted in a decrease in the production of cytokines associated with M1 activation, an increase in cytokine production associated with MSC activation, and an increase in the production of M2 phenotype conversion factors. Therefore, it is suggested that in wound healing, M1 produces cytokines to recruit MSCs to the damaged area, and then MSCs control inflammation while converting M1 to M2 to promote tissue regeneration.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

間葉系幹細胞（MSCs）は，その多分化能や免疫調節能から組織再生の要として着目されてきた.一方で，マクロファージ（Mφ）は自然免疫や組織恒常性維持だけでなく，炎症性Mφ(M1)から抗炎症性Mφ(M2)へと極性を変化することで過剰な免疫を調節し，組織再生を誘導する可能性が示唆されている．しかし，MSCsとMφが創傷治癒過程でどのように関わり，組織再生にどう影響を与えるかはほとんど明らかにされていない．この相互作用を明らかにし, 促進することにより，効率的な歯槽骨再生や，歯周病やインプラント周囲炎などの炎症性疾患の病態形成を抑制する新規治療法の開発に繋がると考えられた．