Improvement of biological functions and therapeutic efficacy of synovial stem cells from osteoarthritis using senolytic drugs

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16708
• 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): 2022-04-01 – 2024-03-31
• Keywords: 細胞老化 / 変形性膝関節症 / 滑膜 / 間葉系幹細胞 / 軟骨

Outline of Final Research Achievements

We attempted to improve quality of synovial mesenchymal stem cells (MSCs) derived from patients with knee osteoarthritis (OA) by using ABT-263, a senolytic drug. Our results showed that ABT-263 treatment reduced the number of senescent cells and improved their ability to form colonies and differentiate into chondrocytes. However, a temporary decrease in proliferative capacity was observed, so we investigated a drug-free method to sort cells based on their size and autofluorescence. MSCs with small size and low autofluorescence showed greater colony formation and chondrogenic differentiation ability than before sorting. We succeeded in a drug-free method to improve synovial MSC quality and are currently engaged in a study to evaluate the biological function and therapeutic efficacy of synovial MSCs purified by this method for OA.

Free Research Field

再生医療、整形外科

Academic Significance and Societal Importance of the Research Achievements

加齢性疾患である変形性膝関節症（OA）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せず、対症療法が行われている。超高齢化を迎えた本邦では、OA治療法の開発は社会的に喫緊の課題である。本研究の成果は、これまでの滑膜間葉系幹細胞（MSCs）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、より患者満足度の高いOA治療法の開発につながると考えられる。また、薬剤を用いない新たなMSCs純化方法により、老化細胞を除去し、MSCsを若返らせる技術を開発できたことから、膝関節を含め様々な分野でのMSCsを用いた再生医療の質の向上につながることが期待される。