Development of efficient treatment of knee osteoarthritis by the combination of senolytic drug and synovial stem cell injection

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17990
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Endo Kentaro 東京医科歯科大学, 統合研究機構, プロジェクト助教 (30844378)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 細胞老化 / 間葉系幹細胞 / 変形性膝関節症 / 関節軟骨 / 半月板 / 滑膜 / 老化細胞除去薬 / ABT-263

Outline of Final Research Achievements

This study showed that the number of senescent chondrocytes and the expression of senescence-associated secretory phenotype (SASP) factor increased over time in a rat osteoarthritis (OA) model. We are currently analyzing whether the therapeutic effect of synovial stem cells is enhanced by the combination with ABT-263. At the same time, we found that meniscus cells also underwent cellular senescence in OA, and discovered a drug that can selectively remove senescent meniscal cells. We also found that ABT-263 can remove senescent cells in synovial stem cells derived from OA patients and improve their biological functions.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

変形性膝関節症（OA）に対する治療法の開発は、有症状者数が多いにも関わらず根本的な治療法が存在しないため、現在社会的に喫緊の課題である。本研究の成果は、これまでの滑膜幹細胞注射によるOA治療効果を老化生物学的観点から向上させることで、より効率的なOA治療法の開発につながる。また、OA発症・進行において非常に重要な半月板を標的とした新しい創薬アプローチにより、OA創薬研究に新規展開をもたらすことが期待される。