Attempt of the periodontal tissue regeneration by the combination of periodontal ligament cell spheroid and vascularization factor

• Project/Area Number: 17K11990
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Periodontology
• Research Institution: Kyushu Dental College
• Principal Investigator: HANATANI TOMOYA 九州歯科大学, 歯学部, 助教 (60649250)
• Co-Investigator(Kenkyū-buntansha): 臼井 通彦 九州歯科大学, 歯学部, 准教授 (10453630)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 歯周再生医学 / 歯学

Outline of Final Research Achievements

With the spheroid, a lot of cells cohered and became in a three-dimensional state. We isolated periodontal ligament cells from a human (hPDLMSCs) withdrawal tooth and we put the human umbilical vein endothelial cells (HUVECs) together and made Co-cultured spheroids.
We confirmed onset of gene of the stemness markers from this co-cultured spheroids from hPDLMSCs and HUVECs. We showed the high expression of bone related genes. Periodontal tissue defects were prepared in the maxillary first molars of rats. The furcation defects were created by removing the alveolar bone, periodontal ligament, and root cementum. Co-cultured spheroids were transplanted into the defects. Treatment with co-cultured spheroids
enhanced alveolar bone, periodontal ligament and new cementum formation after transplantation.

Academic Significance and Societal Importance of the Research Achievements

歯周病は歯周病細菌によって引き起こされる慢性炎症疾患であり、歯と歯肉の付着の喪失や歯槽骨の吸収が生じる。日本での罹患率は成人の７０％以上と報告されており、歯周病による歯周組織破壊が進行すると、歯は脱落し、咬合力の低下による生活の質の低下が問題となる。現在、この破壊された歯周組織を再生させる方法は発表されているが、完全に回復させる治療法は存在しない。その理由として、歯周組織の複雑さがあげられる。
近年、歯根膜細胞に幹細胞が存在し、多分化能を有し、複雑な構造をした歯周組織の各組織に分化する可能性が示唆されており、それが臨床応用できれば、歯周病によって失われた歯周組織の再生が期待される。

Research Products

• [Journal Article] Co-cultured spheroids of human periodontal ligament mesenchymal stem cells and vascular endothelial cells enhance periodontal tissue regeneration (2020)
  • Author(s): Sano Kotaro、Usui Michihiko、Moritani Yuki、Nakazawa Kohji、Hanatani Tomoya、Kondo Hisataka、Nakatomi Mitsushiro、Onizuka Satoru、Iwata Takanori、Sato Tsuyoshi、Togari Akifumi、Ariyoshi Wataru、Nishihara Tatsuji、Nakashima Keisuke
  • Journal Title: Regenerative Therapy Volume: 14 Pages: 59-71
  • DOI: 10.1016/j.reth.2019.12.008
  • Peer Reviewed / Open Access / Int'l Joint Research