Molecular mechanisms of proliferation and differentiation of mesenchymal stem cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10464
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KOGA Hideyuki 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (30594080)
• Co-Investigator(Kenkyū-buntansha): 辻 邦和 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (20323694) ; 宗田 大 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50190864) ; 関矢 一郎 東京医科歯科大学, 統合研究機構, 教授 (10345291)
• Research Collaborator: SEKIYA Ichiro 東京医科歯科大学, 再生医療研究センター, 教授 (10345291)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: MSC / synovium / Proliferation / Differentiation / PI3K / PDGF / chondrogenesis / surface antigen

Outline of Final Research Achievements

Platelet-derived growth factors (PDGFs) have been reported to enhance proliferation of synovial mesenchymal stem cells (MSCs) without reducing their multipotency. This study was aimed to elucidate the intracellular molecular pathways activated by PDGFs. Synovial MSCs were isolated from patients who underwent total knee arthroplasty. Cell proliferation and differentiation assays were performed in the presence of inhibitors specific for intracellular kinases. Both PDGF-AA and -BB enhanced cell proliferation in medium containing reduced serum. These effects were significantly reduced by a PI3K inhibitor, LY290042. During in vitro chondrogenesis, LY290042 significantly reduced the size of spheroids enhanced by PDGF-AA. LY290042 also significantly inhibited in vitro chondrogenic and osteoblastic differentiation. Our data indicated that activation of the PI3K-PKB/Akt pathway by PDGFs plays an important role in both proliferation and differentiation of synovial MSCs.

Free Research Field

間葉系幹細胞生物学