| Project/Area Number |
16K15657
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TSUJI Kunikazu 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)
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| Co-Investigator(Kenkyū-buntansha) |
宗田 大 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (50190864)
関矢 一郎 東京医科歯科大学, 統合研究機構, 教授 (10345291)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 間葉系幹細胞 / 滑膜 / PDGF / PI3K / 細胞増殖 / 軟骨分化 / 表面抗原 / 可塑性 / 増殖 / 分化 / 細胞内シグナル / 全能性 |
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| Outline of Final Research Achievements |
PDGFs have been reported to enhance proliferation of synovial mesenchymal stem cells (MSCs) without reducing their multi-lineage differentiation potential in vitro. This study was aimed to elucidate the intracellular molecular pathways activated by PDGFs. For the purpose of this study, proliferation and differentiation assays were performed in the presence of small inhibitor molecules specific for intracellular kinases.
Both PDGF-AA and -BB enhanced cell proliferation. These effects were significantly reduced by a PI3K inhibitor, LY290042 (LY). During chondrogenic spheroid formation in vitro, LY significantly reduced the size of spheroids enhanced by PDGF-AA. LY also inhibited chondrogenic and osteoblastic differentiation of synovial MSCs.These indicated that activation of the PI3K plays an important role in both proliferation and differentiation of synovial MSCs. Hence, these data could be beneficial for optimizing the in vitro culture conditions of synovial MSCs for clinical use.
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| Academic Significance and Societal Importance of the Research Achievements |
PDGFシグナルは種々の体性幹細胞（間葉系幹細胞）の増殖や分化に関与することが示されている。本研究では、膝滑膜由来間葉系幹細胞の増殖および軟骨、骨分化の両方においてもPDGFシグナルが必須の機能を有していることを示した。また、その細胞内シグナル伝達経路の解析から、PDGFが滑膜MSCsの増殖および分化を促進させる際にPI3Kシグナルが非常に重要な機能を果たしていることを示した。
滑膜由来間葉系幹細胞は、自己細胞移植による関節軟骨や半月板再生への臨床応用研究が期待されている細胞である。本研究結果は、滑膜間葉系幹細胞のin vitro培養条件の最適化に寄与することが期待される。
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