Profiling efficiency of disease-modifying antirheumatic drugs in cartilage regeneration

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08389
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Ehime University
• Principal Investigator: Liu Shuang 愛媛大学, 医学系研究科, 准教授 (60403812)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 間葉系幹細胞 / 関節リウマチ / 軟骨移植 / 免疫抑制薬

Outline of Final Research Achievements

While the concept of MSC-based joint regeneration has promising results and opens new therapeutic possibilities for rheumatoid arthritis (RA) treatment, it is unknown whether antirheumatic drugs administered to RA patients (often continuously) affect the therapeutic efficiency of transplanted MSCs aiming at cartilage repair. To answer this question, we evaluated the effect of major antirheumatic drugs on the multipotency of MSCs. With a special focus on chondrogenic differentiative capacity, a scaffolded chondrospheroid-engrafted murine model was employed for in vivo drug screening. By acknowledging pharmacological, metabolic, and cellular mechanisms, we attempt to provide insight into the contribution of these drugs with regard to healing capacities and MSC-based tissue engineering.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

MSCの誘導分化には免疫微小環境の適正化が必要になる。多くのRA患者は、長期間に渡って様々な作用機序を持つRA治療薬を投与されており、MSCの再生・修復能における安全性評価が必要である。さらに、関節再生医療を受ける患者において、現在受けている抗リウマチ療法が移植されるMSCの再生能に及ぼす影響を把握することが必須である。本研究は、患者自身の滑膜MSCの修復能とMSCを用いる関節軟骨再生医療の二つの面で、網羅的、かつ直接的なエビデンスを入手することができ、MSCを用いるRAの再生治療法の確立に不可欠な先行研究として位置付けられる。