Development of a method to prevent osteonecrosis of the jaw using organoids derived from dental pulp stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09997
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57040:Regenerative dentistry and dental engineering-related
• Research Institution: Keio University
• Principal Investigator: Yasui Takazumi 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (80348771)
• Co-Investigator(Kenkyū-buntansha): 中川 種昭 慶應義塾大学, 医学部(信濃町), 教授 (00227745) ; 森川 暁 慶應義塾大学, 医学部(信濃町), 講師 (00424169) ; 馬渕 洋 藤田医科大学, 医学部, 准教授 (50424172)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 歯髄幹細胞 / 顎骨壊死 / フローサイトメトリー

Outline of Final Research Achievements

We evaluated the usefulness of 3D cultured human dental pulp stem cells (3D hDPSCs) in preventing osteonecrosis of the jaw by transplanting them into the tooth extraction sockets of immunodeficient mice. Transplantation of 2D cultured human dental pulp stem cells (2D hDPSCs) was unable to prevent osteonecrosis of the jaw, but transplantation of 3D hDPSCs covered the tooth extraction socket with epithelium and no bone exposure was observed. Compared to the group transplanted with 2D hDPSCs, the group transplanted with 3D hDPSCs showed bone formation and the rate of empty lacunae was significantly lower. In addition, it was confirmed that 3D hDPSCs expressed high levels of FGF2. These results suggest that FGF2 expressed in 3D hDPSCs contributes to the prevention of osteonecrosis of the jaw.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

薬剤関連顎骨壊死（MRONJ）は、ゾレドロン酸やデノスマブといった骨吸収抑制薬等により生じる顎骨壊死である。MRONJは一般に保存療法では治癒までに期間を要することが多く、外科療法では手術侵襲を伴う。そのために予防が重要となるが、抜歯により発症するリスクが高いため、抜歯時の予防手段を構築する必要がある。本研究では、抜歯時のMRONJ予防における3次元培養した歯髄幹細胞移植の有効性を示す社会的意義のある研究であると考えられた。