Proof of effectiveness of exosomes for regeneration of temporomandibular joint disc and elucidation of regeneration mechanism

• Project/Area Number: 18K17085
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57040:Regenerative dentistry and dental engineering-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nakamura Kaori 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (50817632)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 細胞外微粒子 / 線維軟骨再生 / エクソソーム / 組織再生 / 顎関節関節円板

Outline of Final Research Achievements

MSCs could be isolated from muscle, fat, synovium, and bone marrow, and extracellular microparticles derived from each tissue could be purified. The proliferative capacity of chondrocytes and mesenchymal stem cells was significantly increased (P <0.05) in all of the extracellular microparticle administration group of muscle, adipose, synovial membrane, and bone marrow-derived mesenchymal stem cells as compared with the control group. No significant difference was observed between the extracellular microparticle administration groups. The migration ability of chondrocytes was also significantly increased (P <0.05) in all extracellular particle-administered groups. There was no change in cartilage differentiation potential due to extracellular microparticles. In the histological evaluation of the mouse cartilage defect model, there was a significant improvement in the extracellular microparticle group compared with the control.

Academic Significance and Societal Importance of the Research Achievements

硬組織の再生能を示した細胞外微粒子はMSCsから多く分泌され由来細胞により内容物が異なり、再生能が異なると示唆された。本研究では筋肉、脂肪、滑膜、骨髄からMSCsを単離し培養上清から各組織由来の細胞外微粒子を精製できた。初めて間葉系幹細胞と軟骨細胞に各細胞外微粒子を添加した群と、PBSを添加した群をコントロール群を比較した。
いずれの細胞外微粒子も軟骨細胞と間葉系幹細胞の増殖能と遊走能を向上させた。一方、各細胞外微粒子投与群間での有意な差は認めなかった。軟骨分化能関しては細胞外微粒子による変化はなかった。マウス軟骨再生能は細胞外微粒子群においてコントロールに比較し有意に向上していた。

Research Products

• [Journal Article] Risk factors for residual anterolateral rotational instability after double bundle anterior cruciate ligament reconstruction: Evaluation by quantitative assessment of the pivot shift phenomenon using triaxial accelerometer (2020)
  • Author(s): Katakura Mai、Nakamura Kaori、Watanabe Toshifumi、Horie Masafumi、Nakamura Tomomasa、Katagiri Hiroki、Otabe Koji、Nakagawa Yusuke、Ohara Toshiyuki、Sekiya Ichiro、Muneta Takeshi、Koga Hideyuki
  • Journal Title: The Knee Volume: 27 Issue: 1 Pages: 95-101
  • DOI: 10.1016/j.knee.2019.09.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anatomic femoral tunnel placement is difficult by the transtibial technique: comparison of three different femoral tunnel drilling techniques in double-bundle anterior cruciate ligament reconstructions. (2020)
  • Author(s): Nakamura K1, Nakamura T1, Horie M1, Katagiri H1,2, Otabe K2, Nakagawa Y1,2, Amemiya M1, Sekiya I2, Muneta T1, Koga H3,4
  • Journal Title: Knee Surg Sports Traumatol Arthrosc. Volume: 28 Pages: 584-593
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Initial cell plating density affects properties of human primary synovial mesenchymal stem cells (2018)
  • Author(s): Nakamura Kaori、Tsuji Kunikazu、Mizuno Mitsuru、Koga Hideyuki、Muneta Takeshi、Sekiya Ichiro
  • Journal Title: Journal of Orthopaedic Research? Volume: - Issue: 6 Pages: 1358-1367
  • DOI: 10.1002/jor.24112
  • Peer Reviewed
• [Presentation] 人工膝関節置換術（TKA）での組織軟部バランスが術後の関節可動域に与える影響 (2020)
  • Author(s): 中村 香織
  • Organizer: 日本人工関節学会
• [Presentation] Is a grafted tendon flattened at the tunnel aperture after anatomical flat anterior cruciate ligament reconstruction using hamstring autograft? (2019)
  • Author(s): Hayashi M., Yoshimura H., Ogiuchi T., Takahashi T., Matsumura E., Nakamura K., Uomizu M., Hasegawa S., Seki R., Hoshino A.
  • Organizer: ESSKA Speciality Days
  • Int'l Joint Research
• [Presentation] The effect of tight medial patellofemoral ligament fixation (2019)
  • Author(s): Nakamura K., Hayashi M., Ogiuchi T., Yoshimura H., Takahashi T., Matsumura E., Uomizu M., Hasegawa S., Seki R., Hoshino A.
  • Organizer: ESSKA Speciality Days
  • Int'l Joint Research
• [Presentation] Effect of ACL Reconstruction and Meniscus Repair on Anterolateral Rotational Instability of the ACL Injured Knee: Quantitative Assessment of the Pivot Shift Phenomenon Using Triaxial Accelerometer. (2018)
  • Author(s): Mai Katakura, Hideyuki Koga, Ichiro Sekiya, Toshifumi Watanabe, Masafumi Horie,Hiroki Katagiri,Koji Otabe, Toshiyuki Ohara, Kaori Nakamura, Kenta Katagiri, Hiroko Ueki, Takeshi Muneta.
  • Organizer: Orthopaedic Research Society 2018 Annual Meeting
  • Int'l Joint Research