Prediction of cells indicating superior regenerative potential for allogeneic transplantation of periodontal ligament cells

• Project/Area Number: 17K17346
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Periodontology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Tsumanuma Yuka 東京医科歯科大学, 大学院医歯学総合研究科, プロジェクト助教 (70726265)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 歯根膜由来間葉系幹細胞 / 歯根膜細胞 / 同種移植 / 間葉系幹細胞 / 歯根膜

Outline of Final Research Achievements

Using cells with high quality for the allogeneic transplantation might provide the superior tissue regeneration. It is need to decide what kind of cells should be selected before transplantation. In this study, we performed the primary culture of human periodontal ligament derived mesenchymal stromal cells (PDL-MSCs) and compared the cell property. The result is that the PDL-MSCs show the different property in vitro by donor. Cell morphology imaging of PDL-MSCs by cell florescence staining and analysis of the area of cytoplasm using florescence microscope showed the difference upon osteogeneic induction.
These results demonstrate that the cells using for the allogeneic transplantation can be selected and predict the regenerative potential of cells.

Academic Significance and Societal Importance of the Research Achievements

同種の細胞を用いた臨床研究が主流となりつつあり中で、どのような細胞を選択し、移植に用いればより再生能が高い結果が得られるかは不明な点が多い。本研究ではあらかじめ移植する前の歯根膜由来MSCの再生能を予測可能かどうかを明らかにすることに着目した。in vitroで計測可能な特性の検討を行い、その特性の組み合わせにより歯根膜由来MSC固有の再生能予測基準を決定することで、再生能が高い細胞と低い細胞に分別する事が可能となる。この結果、再生能が高い細胞をあらかじめ予測選択し、移植に用いることで、同種細胞移植治療の実現および普及に貢献可能と考えられる。

Research Products

• [Journal Article] Allogeneic multipotent mesenchymal stromal cell sheet transplantation promotes healthy healing of wounds caused by zoledronate and dexamethasone in canine mandibular bones (2019)
  • Author(s): KAIBUCHI Nobuyuki†, IWATA Takanori, ONIZUKA Satoru, YANO Kosei, TSUMANUMA Yuka, YAMATO Masayuki, OKANO Teruo, ANDO Tomohiro
  • Journal Title: Regenerative Therapy Volume: 10 Pages: 77-83
  • DOI: 10.1016/j.reth.2018.10.008
  • Peer Reviewed / Open Access
• [Journal Article] Application of cell-sheet engineering for new formation of cementum around dental implants (2019)
  • Author(s): Iwasaki Kengo、Washio Kaoru、Meinzer Walter、Tsumanuma Yuka、Yano Kosei、Ishikawa Isao
  • Journal Title: Heliyon Volume: 5 Issue: 6 Pages: e01991-e01991
  • DOI: 10.1016/j.heliyon.2019.e01991
  • Peer Reviewed / Open Access
• [Journal Article] In Vivo Periodontium Formation Around Titanium Implants Using Periodontal Ligament Cell Sheet. (2018)
  • Author(s): Washio K, Tsutsumi Y, Tsumanuma Y, Yano K, Srithanyarat Supreda S, Takagi R, Ichinose S, Meinzer W, Yamato M, Okano T, Hanawa T, Ishikawa I
  • Journal Title: Tissue Engineering Part A Volume: 24 Issue: 15-16 Pages: 1273-1282
  • DOI: 10.1089/ten.tea.2017.0405
  • Peer Reviewed
• [Journal Article] Periodontal regeneration with autologous periodontal ligament-derived cells sheets - A safety and efficacy study in ten patients. (2018)
  • Author(s): Iwata T, Yamato M, Washio K, Yoshida T, Tsumanuma Y, Yamada A, Onizuka S, Izumi Y, Ando T, Okano T, Ishikawa I.
  • Journal Title: Regenerative Therapy Volume: 9 Pages: 38-44
  • DOI: 10.1016/j.reth.2018.07.002
  • Peer Reviewed / Open Access
• [Presentation] 同種歯根膜由来間葉系幹細胞シートによる歯周組織の再建 (2019)
  • Author(s): 岩田隆紀, 鬼塚 理, 妻沼有香, 朴 聖俊, 中井謙太, 安藤智博
  • Organizer: 第18回日本再生医療学会総会
• [Presentation] The establishment of safety and efficacy evaluation for allogeneic periodontal ligament derived multipotent mesenchymal stromal cell sheet with next-generation sequencer (2018)
  • Author(s): Iwata T, Onizuka S, Park S, Tsumanuma Y, Nakai K, Izumi Y, Ando T
  • Organizer: TERMIS World Congress 2018
  • Int'l Joint Research
• [Presentation] 同種歯根膜由来間葉系幹細胞シートによる歯周組織の再建 (2018)
  • Author(s): 岩田隆紀, 鬼塚理, 妻沼有香, 朴聖俊, 中井謙太, 安藤智博
  • Organizer: 第18回日本再生医療学会総会
• [Presentation] 同種歯根膜細胞シートの安全性・有効性評価指標の確立と歯周組織の再建 (2018)
  • Author(s): 岩田 隆紀, 鬼塚 理, 朴 聖俊, 妻沼 有香, 和泉 雄一, 中井 謙太, 安藤 智博
  • Organizer: 第17回日本再生医療学会総会