Investigation of allogeneic synovial mesenchymal stem cells for cartilage and meniscus regeneration therapy

• Project/Area Number: 15H04953
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SEKIYA Ichiro 東京医科歯科大学, 統合研究機構, 教授 (10345291)
• Co-Investigator(Kenkyū-buntansha): 辻 邦和 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (20323694)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 移植・再生医療 / 再生医療

Outline of Final Research Achievements

Conflicting evidence exists regarding the immunosuppressive capacity of mesenchymal stem cells (MSCs). Our aim was to examine the effects of inducing recipient T cell responses by dead allogeneic MSCs and of suppressing the responses by living MSCs. Synovial fluid (SF) was obtained from patients who underwent knee surgeries. SF mononuclear cells were co-cultured with dead allogeneic MSCs. Immunosuppressive capacity of MSCs was verified by the addition of living MSCs to the co-culture. CD141+ dendritic cells and CD141lowCD11b+CD14+ macrophages were identified in patient SF. Dead allogeneic MSCs were taken up by synovial APCs and induced T cell proliferation and cytokine production such as granzyme B and IL-6. Addition of living MSCs counteracted T cell proliferation and granzyme B production. Dead allogeneic MSCs elicited cytotoxic T cell responses with the help of Th1 cytokines but living MSCs counteract this and direct intra-articular environment to anti-inflammatory condition.

Research Products

• [Journal Article] ヒト幹指針開始前・後から再生医療新法に至る整形外科領域の再生医療 その進捗と今後の展望 滑膜幹細胞による軟骨・半月板を対象とした再生医療 (2017)
  • Author(s): 関矢 一郎, 宗田 大
  • Journal Title: 日本整形外科学会雑誌 Volume: 91 Pages: 223-227
• [Journal Article] 【OAの最新治療-関節再生を目指して-】 滑膜由来幹細胞移植による半月板再生 (2017)
  • Author(s): 関矢一郎
  • Journal Title: 分子リウマチ治療 Volume: 10 Pages: 71-74
• [Journal Article] 【診断と治療のABC[122]変形性関節症】 (第5章)外科療法 再生医療 滑膜幹細胞移植 (2017)
  • Author(s): 関矢一郎
  • Journal Title: 最新医学(別冊変形性関節症) Volume: - Pages: 226-233
• [Journal Article] 【再生医療の基礎と臨床】半月板の再生医療 (2017)
  • Author(s): 関矢一郎
  • Journal Title: BIO Clinica Volume: 32 Pages: 978-982
• [Journal Article] 滑膜間葉系幹細胞の定期的関節内投与は変形性膝関節症の進行を抑制する (2017)
  • Author(s): 大関 信武, 宗田 大, 齋藤 知行, 関矢 一郎
  • Journal Title: 再生医療 Volume: 16 Pages: 241-248
• [Journal Article] 膝関節内病変に対する細胞治-その理論的根拠と基礎から臨床への展開- (2017)
  • Author(s): 関矢一郎
  • Journal Title: 関節外科 Volume: 36 Pages: 31-41
• [Journal Article] Pretreatment with IL1β enhances proliferation and chondrogenic potential of synoviumderived mesenchymal stem cells. (2017)
  • Author(s): Matsumura E
  • Journal Title: Cytotherapy. Volume: 19(2) Issue: 2 Pages: 181193-181193
  • DOI: 10.1016/j.jcyt.2016.11.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Yields and chondrogenic potential of primary synovial mesenchymal stem cells are comparable between rheumatoid arthritis and osteoarthritis patients. (2017)
  • Author(s): Yuji Kohno, Mitsuru Mizuno, Nobutake Ozeki, Hisako Katano, Keiichiro Komori, Shizuka Fujii, Koji Otabe, Masafumi Horie, Hideyuki Koga, Kunikazu Tsuji, Mikio Matsumoto, Haruka Kaneko, Yuji Takazawa, Takeshi Muneta, Ichiro Sekiya
  • Journal Title: Stem Cell Res Ther Volume: 8 Issue: 1 Pages: 115-115
  • DOI: 10.1186/s13287-017-0572-8
  • Peer Reviewed / Open Access
• [Journal Article] TNFα promotes proliferation of human synovial MSCs while maintaining chondrogenic potential. (2017)
  • Author(s): Shioda M, Muneta T, Tsuji K, Mizuno M, Komori K, Koga H, Sekiya I.
  • Journal Title: PLoS One Volume: 12 Issue: 5 Pages: e0177771-e0177771
  • DOI: 10.1371/journal.pone.0177771
  • Peer Reviewed / Open Access
• [Journal Article] Inflammatory cytokine levels in synovial fluid 3, 4 days postoperatively and its correlation with early-phase functional recovery after anterior cruciate ligament reconstruction: a cohort study. (2016)
  • Author(s): Inoue M, Muneta T, Ojima M, Nakamura K, Koga H, Sekiya I, Okazaki M, Tsuji K.
  • Journal Title: J Exp Orthop. Volume: 3 Issue: 1 Pages: 30-38
  • DOI: 10.1186/s40634-016-0067-z
  • Peer Reviewed / Open Access
• [Journal Article] 3.Arthroscopic transplantation of synovial stem cells improves clinical outcomes in knees with cartilage defects. (2015)
  • Author(s): Ichiro Sekiya, Takeshi Muneta, Masafumi Horie, Hideyuki Koga
  • Journal Title: Clin Orthop Relat Res. Volume: 473 Issue: 7 Pages: 2316-2326
  • DOI: 10.1007/s11999-015-4324-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 間葉系幹細胞による変形性膝関節症(半月板・軟骨)の再生医療 (2017)
  • Author(s): 関矢 一郎
  • Organizer: 再生医療産学官連携シンポジウム
• [Presentation] 膝痛を再生医療で治す！アカデミアの挑戦 (2017)
  • Author(s): 関矢 一郎
  • Organizer: DIA日本年会
• [Presentation] 変形性膝関節症の定量評価と再生医療 (2017)
  • Author(s): 関矢一郎
  • Organizer: 日本リウマチ学会北海道・東北支部学術集会
• [Presentation] Dynamic analysis of inflammatory cells in synovial fluid after index anterior cruciate ligament reconstruction surgery (2016)
  • Author(s): Kaori Nakamura, Kunikazu Tsuji, Hiroki Katagiri, Makiko Inoue, Miyoko Ojima, Ichiro Sekiya, Takeshi Muneta
  • Organizer: Osteoarthritis Research Society International
  • Place of Presentation: Amsterdam(Netherlands)
  • Year and Date: 2016-03-31
  • Int'l Joint Research
• [Presentation] 滑膜由来間葉系幹細胞を特徴付ける表面抗原の網羅的解析 (2016)
  • Author(s): 辻 邦和、尾島美代子、小田邉浩二、堀江雅史、古賀英之、関矢一郎、宗田 大
  • Organizer: 軟骨代謝学会
  • Place of Presentation: 広仁会館（広島県広島市）
  • Year and Date: 2016-02-19
• [Presentation] 滑膜由来間葉系幹細胞を特徴付ける表面抗原の網羅的解析 (2015)
  • Author(s): 辻 邦和、尾島美代子、小田邉浩二、堀江雅史、古賀英之、関矢一郎、宗田 大
  • Organizer: 日本運動器移植、再生医学研究会
  • Place of Presentation: ANAクラウンプラザホテル（山口県宇部市）
  • Year and Date: 2015-09-25
• [Presentation] 細胞剥離法の差異が滑膜由来間葉系幹細胞の表面抗原解析の結果に及ぼす影響 (2015)
  • Author(s): 尾島美代子、辻邦和、小田邉浩二、 堀江雅史、古賀英之、 関矢一郎、宗田 大
  • Organizer: 日本運動器移植、再生医学研究会
  • Place of Presentation: ANAクラウンプラザホテル（山口県宇部市）
  • Year and Date: 2015-09-25