Elucidate the molecular mechanism of pain suppression and cartilage protection by mesenchymal stem cells in a rabbit arthritis model

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09513
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: ICHISEKI Toru 金沢医科大学, 医学部, 教授 (30307631)
• Co-Investigator(Kenkyū-buntansha): 島崎 都 金沢医科大学, 医学部, 講師 (00440511) ; 上田 善道 金沢医科大学, 医学部, 教授 (50271375)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 骨髄間葉系幹細胞 / ホーミング / 軟骨 / モノヨード酢酸 / CXCL12/CXCR4

Outline of Final Research Achievements

The effects of MSCs on the prevention of cartilage damage and pain suppression were investigated in an animal model. Expression of C-X-C motif chemokine ligand 12 (CXCL12), which is involved in homing of bone marrow mesenchymal stem cells (BM-MSCs), was observed in injured cartilage tissue, suggesting that homing to cartilage tissue is expected. Expression of TNF-α induced protein 6 (TSG6), a chondroprotective factor released from BM-MSCs, was also observed in damaged cartilage. In addition, treatment with BM-MSCs suppressed the expression of calcitonin gene-related peptide (CGRP) in the dorsal horn of the spinal cord.
BM-MSCs also maintained mitochondrial function and showed sufficient ATP production under hypoxic stress conditions that induced osteocyte death. This suggests that BM-MSCs are sufficiently effective against hypoxic conditions in tissues such as cartilage and bone tissue.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

高齢化社会の現在、変形性関節症の罹患率は非常に増加している。本疾患の予防や、本疾患による疼痛改善は、今後も高齢化が進む日本において最重要課題である。今回の研究からBM-MSCの関節内投与および経静脈投与により損傷した軟骨組織へのMigration/Homingを認め、疼痛改善効果も確認できた。本研究結果は、今後の再生医療や予防医学を含むBM-MSCの治療方法の応用に非常に役立つと考えられた。