Roles of macrophage exosomes in biological signals that induce tissue regeneration

• Project/Area Number: 18K09738
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Fujihara Yuko 東京大学, 医学部附属病院, 客員研究員 (50466744)
• Co-Investigator(Kenkyū-buntansha): 石橋 牧子 東京大学, 医学部附属病院, 客員研究員 (60802395) ; 星 和人 東京大学, 医学部附属病院, 教授 (30344451)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 組織再生 / マクロファージ / エクソソーム / 軟骨再生医療 / 再生軟骨

Outline of Final Research Achievements

The purpose of this study was to clarify the role of exosomes in transplantation of tissue-engineered cartilage and to elucidate the process of tissue maturation from the interaction between chondrocytes and macrophages.
Exosomes were isolated from the culture medium of human auricular chondrocytes and mouse macrophage-like cell, RAW264. The obtained exosomes were added to culture media of chondrocytes and RAW264, respectively. Gene expressions in chondrocytes and RAW264 were analyzed by real-time RT PCR. It was suggested that chondrocyte-derived exosomes induced both M1 and M2 macrophages toward M2, and macrophage-derived exosomes promoted chondrocyte differentiation.

Academic Significance and Societal Importance of the Research Achievements

再生医療において、移植後の組織成熟や安定化を実現するためには、再生組織に対する組織反応を把握し制御していく必要がある。われわれはこれまでの検討で、ポリ乳酸足場素材と耳介軟骨細胞で構成される再生軟骨組織をマウスへ移植し、移植後の再生軟骨組織に局在するホスト由来細胞がマクロファージであること、再生軟骨の成熟が進行する移植後1-2週にかけて、マクロファージの局在が増加することなどを明らかにした。本研究では、軟骨細胞とマクロファージそれぞれが分泌するエクソソームが互いの細胞特性に影響を与えつつ組織成熟が進行していく可能性が示され、生体に移植された再生軟骨組織の組織形成過程解明の一助となったと考える。

Research Products

• [Journal Article] Requirement of direct contact between chondrocytes and macrophages for the maturation of regenerative cartilage. (2021)
  • Author(s): Kengo Kanda, Yukiyo Asawa, Ryoko Inaki, Yuko Fujihara, Kazuto Hoshi, Atsuhiko Hikita
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 22476-22476
  • DOI: 10.1038/s41598-021-01437-6
  • Peer Reviewed / Open Access
• [Journal Article] Controlling the Phenotype of Macrophages Promotes Maturation of Tissue-Engineered Cartilage. (2020)
  • Author(s): Fujihara Y, Abe T, Hoshi K.
  • Journal Title: Tissue Eng Part A. Volume: in press Issue: 17-18 Pages: 1005-1013
  • DOI: 10.1089/ten.tea.2019.0190
  • Peer Reviewed
• [Journal Article] Influence of Damage-Associated Molecular Patterns from Chondrocytes in Tissue-Engineered Cartilage (2020)
  • Author(s): Fujihara Yuko、Abe Takahiro、Asawa Yukiyo、Nishizawa Satoru、Saijo Hideto、Hikita Atsuhiko、Hoshi Kazuto
  • Journal Title: Tissue Engineering Part A Volume: 00 Issue: 1-2 Pages: 1-9
  • DOI: 10.1089/ten.tea.2019.0185
  • Peer Reviewed / Open Access
• [Presentation] 再生軟骨移植におけるダメージ関連分子パターン(DAMPs)の影響． (2022)
  • Author(s): 藤原夕子，疋田温彦，星和人．
  • Organizer: 第21回日本再生医療学会総会
• [Presentation] 唇裂鼻変形の患者に対する再生軟骨移植の画像診断を用いた有効性評価 (2018)
  • Author(s): 藤原夕子、西條英人、倉林くみ子、末永英之、稲木涼子、杉山円、米永一理、高戸毅、星和人
  • Organizer: 第63回日本口腔外科学会総会・学術大会