Localization analysis of synovial mesenchymal stem cells aimed for the technological development of cartilage and meniscus regenerative medicine

• Project/Area Number: 26893066
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Mizuno Mitsuru 東京医科歯科大学, 再生医療研究センター, 特任研究員 (00733908)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 再生医療 / 滑膜幹細胞 / 変形性膝関節症 / 滑膜組織 / 半月板 / 関節軟骨 / 再生医学 / 間葉系幹細胞 / 局在解析 / 軟骨再生 / 再生医療技術

Outline of Final Research Achievements

In Japan, which has become a super-aged society, to develop a superior regenerative medical technology for meniscal damage and cartilage degeneration associated with knee osteoarthritis is awaited by huge number of the patients estimated to be about 8.5 million. In this research, we tried to develop basic technologies based on the characteristics by performing identification to the localization of synovial mesenchymal stem cells and functional analysis of purified cells. We have suggested the localization of the synovial stem cells and presented the results at the 15th The Japanese Society for Regenerative Medicine. In addition, we have been developed stem cell culture methods for clinical cell transplantation study using human serum, which was instability and high safety material, by the functional analysis of purified cells. Then, we have published its research achievements in “Stem cell research and therapy” that was peer reviewed in English.

Research Products

• [Journal Article] Cartilage derived from bone marrow mesenchymal stem cells expresses lubricin in vitro and in vivo (2016)
  • Author(s): Yusuke Nakagawa, Takeshi Muneta, Koji Otabe, Nobutake Ozeki, Mitsuru Mizuno, Mio Udo, Ryusuke Saito, Katsuaki Yanagisawa, Shizuko Ichinose, Hideyuki Koga, Kunikazu Tsuji and Ichiro Sekiya
  • Journal Title: PLoS ONE Volume: 11 Issue: 2 Pages: e0148777-e0148777
  • DOI: 10.1371/journal.pone.0148777
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats. (2016)
  • Author(s): Ozeki N, Muneta T, Koga H, Nakagawa Y, Mizuno M, Tsuji K, Mabuchi Y, Akazawa C, Kobayashi E, Matsumoto K, Futamura K, Saito T, Sekiya I
  • Journal Title: Osteoarthritis Cartilage Volume: in press Issue: 6 Pages: 1061-70
  • DOI: 10.1016/j.joca.2015.12.018
  • NAID: 40021330438
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates. (2016)
  • Author(s): Kondo S, Muneta T, Nakagawa Y, Koga H, Watanabe T, Tsuji K, Sotome S, Okawa A, Kiuchi S, Ono H, Mizuno M, Sekiya I
  • Journal Title: J Orthop Res Volume: in press Issue: 6 Pages: 1274-1282
  • DOI: 10.1002/jor.23211
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Platelet-derived growth factor (PDGF)-AA/AB in human serum are potential indicators of the proliferative capacity of human synovial mesenchymal stem cells. (2015)
  • Author(s): Mizuno M, Katano H, Otabe K, Komori K, Matsumoto Y, Fujii S, Ozeki N, Tsuji K, Koga H, Muneta T, Matsuyama A, Sekiya
  • Journal Title: Stem Cell Res Ther. Volume: 10 Issue: 1 Pages: 243-243
  • DOI: 10.1186/s13287-015-0239-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Synovial mesenchymal stem cells promote healing after meniscal repair in microminipigs. (2015)
  • Author(s): Nakagawa Y, Muneta T, Kondo S, Mizuno M, Takakuda K, Ichinose S, Tabuchi T, Koga H, Tsuji K, Sekiya I.
  • Journal Title: Osteoarthritis Cartilage. Volume: in press Issue: 6 Pages: 1007-1017
  • DOI: 10.1016/j.joca.2015.02.008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Synovial mesenchymal stem cells promote meniscus regeneration augmented by an autologous Achilles tendon graft in a rat partial meniscus defect model (2015)
  • Author(s): N. Ozeki, T. Muneta, S. Matsuta, M. Mizuno, et al.
  • Journal Title: Stem Cells Volume: in press
  • Peer Reviewed / Open Access
• [Presentation] PDGF-AA/AB in human serum are potential indicators of the proliferative capacity of human synovial mesenchymal stem cells (2016)
  • Author(s): Mitsutu Mizuno, Hisako Katano, Koji Otabe, Keiiciro Komori, Yukie Matsumoto, Nobutake Ozeki, Kunikazu Tsuji, Takeshi Muneta, Ichiro Sekiya
  • Organizer: Orthopaedic Research Society 2016 Annual Meeting
  • Place of Presentation: Orlando, Florida (USA)
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] Properties of MSCs derived from Surface, Stroma, and Perivascular synovium of OA patients (2016)
  • Author(s): Mitsutu Mizuno, Hisako Katano, Yo Mabuchi, Yusuke Ogata, Shizuko Ichinose, Koji Otabe, Keiiciro Komori, Yukie Matsumoto, Nobutake Ozeki, Kunikazu Tsuji, Chiro Akazawa, Takeshi Muneta, Ichiro Sekiya
  • Organizer: Orthopaedic Research Society 2016 Annual Meeting
  • Place of Presentation: Orlando, Florida (USA)
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] 緩徐に凝集させ分離したヒト血清はPDGF-AA濃度が増し滑膜幹細胞の増殖を強める (2015)
  • Author(s): 水野 満、宗田 大、小森 啓一郎、片野 尚子、松本 幸恵、小田邉 浩二、辻 邦和、大川 淳、関矢 一郎
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 富山国際会議場ほか（富山市, 富山）
  • Year and Date: 2015-10-22
• [Presentation] 滑膜幹細胞を用いたヒト血清の増殖性を予測する因子の探索 (2015)
  • Author(s): 水野 満
  • Organizer: 第36回日本炎症・再生医学会
  • Place of Presentation: 虎ノ門ヒルズフォーラム（東京）
  • Year and Date: 2015-07-21 – 2015-07-22
• [Presentation] 滑膜幹細胞の増殖を促進するヒト血清分離法の工夫 (2015)
  • Author(s): 水野 満、小森 啓一郎、片野 尚子、松本 幸恵、小田邉 浩二、 関矢 一郎
  • Organizer: 第36回日本炎症・再生医学会
  • Place of Presentation: 虎ノ門ヒルズフォーラム（港区, 東京）
  • Year and Date: 2015-07-21
• [Presentation] 滑膜幹細胞増殖を予測する自己血清評価法の確立 (2015)
  • Author(s): 水野 満
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜（神奈川）
  • Year and Date: 2015-03-19 – 2015-03-21