Development of the tendon/ligament regenerative therapy utilizing human multipotent periodontal ligament stem cells

• Project/Area Number: 15K11234
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: OKUBO Naoto 北海道大学, 薬学研究院, 特任助教 (00553207)
• Co-Investigator(Kenkyū-buntansha): 北川 善政 北海道大学, 歯学研究院, 教授 (00224957)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 再生医療 / 組織幹細胞 / 歯根膜幹細胞 / 靭帯再生 / 腱再生 / 組織再生 / 三次元培養 / 靭帯・腱

Outline of Final Research Achievements

We previously reported that Periodontal ligament stem cells(PDLSCs) possess the capacity to construct three-dementional blood vessel structures in vitro and can differentiate into the activated fibloblasts called myofibloblasts, which is essential for wound healing process.
Here in this study, we report that PDLSCs can construct there-dementional ligament like structure in vitro to utilizing the collagen gel contractile activity which produced when PDLSCs differented into myofibrobrasts. This constructed ligament like structure not only has dense collagen fibers that parallel to one another but possess physical strength not to break off when it pilled both sides with fingers. These promising results suggesting that PDLSCs may provide a new therapeutic application for ligament/tendon regenerative therapy.

Research Products

• [Journal Article] IL-1β and TNF-α suppress TGF-β-promoted NGF expression in periodontal ligament-derived fibroblasts through inactivation of TGF-β-induced Smad2/3-, and p38 MAPK-mediated signals. (2018)
  • Author(s): Ohta M., Chosa N., Kyakumoto S., Yokota S., Okubo N., Nemoto A., Kamo M., Joh S., Satoh K., Ishisaki A.
  • Journal Title: International Journal of Molecular Medicine Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Bone marrow-derived mesenchymal stem cells propagate immunosuppressive/anti-inflammatory macrophages in cell-to-cell contact-independent and -dependent manners under hypoxic culture (2017)
  • Author(s): Takizawa N, Okubo N, Kamo M, Chosa N, Mikami T, Suzuki K, Yokota S, Ibi M, Ohtsuka M, Taira M, Sasaki D, Yaegashi T, Ishisaki A, Kyakumoto S
  • Journal Title: Experimental Cell Res. Volume: 358 Issue: 2 Pages: 411-420
  • DOI: 10.1016/j.yexcr.2017.07.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MICROCRACKS DESIGN AND BONE INDUCTION OF SKULL BONE MODIFIED BY ULTRASONIC TREATMENT USING ACIDIC ELECTROLYZED WATER (2017)
  • Author(s): Shakya M., Murata M., Okubo N., Nagayasu H., Akazawa T.
  • Journal Title: Phosphorus Research Bulletin Volume: 33 Issue: 0 Pages: 1-6
  • DOI: 10.3363/prb.33.1
  • NAID: 130005628661
  • ISSN: 0918-4783, 1882-2363
  • Peer Reviewed
• [Journal Article] PIAS3 enhances the transcriptional activity of HIF-1α by increasing its protein stability. (2016)
  • Author(s): Nakagawa K, Kohara T, Uehata Y, Miyakawa Y, Sato-Ueshima M, Okubo N, Asaka M, Takeda H, Kobayashi M
  • Journal Title: Biochemical and Bioohysical Research Communications Volume: 469 Issue: 3 Pages: 470-476
  • DOI: 10.1016/j.bbrc.2015.12.047
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] マウス骨髄由来培養細胞において間葉系幹細胞は未分化単球／マクロファージを免疫抑制性マクロファージへと誘導する：細胞接着の関与. (2017)
  • Author(s): 客本斉子、滝沢尚希、大久保直登、鈴木啓太、帖佐直幸、衣斐美歩、加茂政晴、八重柏隆、石崎明
  • Organizer: 第58回歯科基礎医学会学術大会
• [Presentation] 自家象牙質移植による再生骨の組織学的証拠． (2017)
  • Author(s): 村田 勝，横関健治，Shakya Mamata，南田康人，草野 薫，大久保直登，赤澤敏之，永易裕樹．
  • Organizer: 第26回硬組織再生生物学会
• [Presentation] ラット歯根膜幹細胞由来筋線維芽細胞の収縮作用による歯周免疫機構への物理的関与． (2017)
  • Author(s): 大久保直登，村田 勝，赤澤敏之，中川宏治，帖佐直幸，武田宏司，石崎 明．
  • Organizer: 第26回硬組織再生生物学会
• [Presentation] Bone induction on surface of rat compact bone treated with ultrasonic irradiation and acidic electrolyzed water. (2017)
  • Author(s): Mamata Shakya, Masaru Murata, Kenji Yokozeki, Naoto Okubo, Toshiyuki Akazawa, Hiroki Nagayasu
  • Organizer: 第26回硬組織再生生物学会
• [Presentation] マウス骨髄由来間葉系幹細胞は共培養下で未分化単球／マクロファージ系細胞を CD206 陽性の免疫抑制性(M2)マクロファージに分化誘導する. (2017)
  • Author(s): 客本齊子、滝沢尚希、島 杏奈、帖佐直幸、加茂政晴、大久保直登、衣斐美歩、八重柏隆、石崎 明
  • Organizer: 第57回歯科基礎医学会学術大会
• [Presentation] Mesenchymal stem cells educate undifferentiated monocyte/macrophages to the M2 macrophages in cell-cell adhesion-dependent and independent ways. (2017)
  • Author(s): Naoki Takizawa, Naoto Okubo, Masaharu Kamo, Naoyuki Chosa, Toshinari Mikami, Keita Suzuki, Seiji Yokota, Miho Ibi, Masato Otuka, Masayuki Taira, Daisuke Sasaki, Takashi Yaegashi , Akira Ishisaki, Seiko Kyakumoto
  • Organizer: 第65回国際歯科研究学会日本部会（JADR）学術大会
  • Int'l Joint Research
• [Presentation] Bone marrow-derived mesenchymal stem cells propagate immunosuppressive/anti-inflammatory macrophages in cell-to-cell contact-independent and -dependent manners under hypoxic culture. (2017)
  • Author(s): Seiko Kyakumoto, Naoki Takizawa, Naoto Okubo, Masaharu Kamo, Naoyuki Chosa, Seiji Yokota, Masato Ohtsuka, Miho Ibi, Takashi Yaegashi, Akira Ishisaki
  • Organizer: 第40回日本分子生物学会年会