Treatment and reconstruction for osteonecrosis of the jaw using cell sheet combined with titanium reconstruction plate

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18681
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Kaibuchi Nobuyuki 東京女子医科大学, 医学部, 講師 (50621330)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ビスホスホネート / BRONJ / 顎骨壊死 / MRONJ / 間葉系幹細胞 / 細胞シート / 再生医療等製品 / デノスマブ

Outline of Final Research Achievements

Beagle dog experiments were planned as translational research to advance a novel treatment for bisphosphonate-related osteonecrosis of the jaw (BRONJ) using mesenchymal stromal cell sheets (MSC sheets) into clinical research. We were able to create a beagle dog model of BRONJ by administering zoledronic acid and dexamethasone, debridement of the gingiva, and shaving of the jaw bone. In the future, they will conduct experiments to implant periodontal ligament-derived MSC sheets into this model. As an extension of this treatment, we developed a biocompatible plate reconstruction for severe cases. When titanium plates with MSC sheets were implanted in rats treated with zoledronic acid and dexamethasone, inflammation was significantly suppressed compared to the control group.

Free Research Field

口腔外科学、再生医学

Academic Significance and Societal Importance of the Research Achievements

BRONJに対する顎骨を切除する手術は高確率に根治可能であるが、術後の摂食・嚥下障害、構音障害、顔面の形態異常などQOLの大きな喪失は避けられない。MSCシートによる治療は比較的低侵襲に治療を行える、手術に代わる治療法として期待できる。本研究ではこの治療法の臨床応用に向けてビーグル犬を用いたトランスレーショナルリサーチを計画した。また、BRONJの手術後の再建方法も現状のプレート再建では感染や再発のリスクがあり、原因薬剤や基礎疾患から自家骨移植は困難なことが多い。本研究で開発したMSCシートを用いた新規プレート再建法はこの問題を解決する画期的な再建法となりえる。