| Project/Area Number |
17K11559
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Plastic surgery
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| Research Institution | Kindai University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 脂肪由来間葉系間質幹細胞 / 解糖系代謝 / シグナル伝達 / 再生医療 / ３次元皮膚構築 / 脂肪由来間葉系幹細胞 / 幹細胞マーカー / 3次元皮膚 / 間葉系幹細胞 / 脂肪 / 解糖系 / 低酸素 / Notchシグナル / p53 / NF-kB / 低酸素応答 / 幹細胞 / 嫌気的解糖 / ヒト脂肪組織間葉系幹細胞 / 糖代謝 |
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| Outline of Final Research Achievements |
We identified a group of key genes responsible (a master regulators) for the hypoxia response in adipose-derived mesenchymal stromal/stem cells, and were selected characteristic marker expressing on cell surface. By further segregation of these cell subgroups, we found that they tend to differentiate into various terminal differentiated cells especially belonging to the mesenchymal lineage. This led to the isolation of a subpopulation of Hx-hASCs that are proficient in adipocyte differentiation using the master regulator as an indicator, and the narrowing down to a sharpening of the subpopulation for the unique hASCs. In addition, we found that the synergistic effect of fibroblasts on the maintenance of epithelial cells, such as keratinocytes, and the qualitative and quantitative balance between fibroblasts and the adipose-derived mesenchymal stem cell subgroups affect the turnover of the dermal layer, albeit at a preliminary level in the basic study of the artificial skin 3D model.
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| Academic Significance and Societal Importance of the Research Achievements |
脂肪由来間葉系幹細胞は培養を施されることによる選択的なバイアスがかかることが大きな障壁であった。ゆえに、生体内の生存環境のなかでも低酸素領域を好む脂肪由来間葉系幹細胞について、その幹細胞性の維持機構の解明は、極めて重要な知見となる。本研究では、脂肪由来幹細胞におけるNotch-低酸素応答シグナルが制御する解糖系亢進メカニズムに関わる責任遺伝子群の選別に成功し、間葉系に属する各種の終末細胞への分化特性に傾向があることを見出した。面白い事に、この亜集団はヒト表皮組織が豊潤に分化成熟することもわかった。以上の結果や知見は、真の脂肪由来幹細胞の同定と生体内での機能の理解への一助を照らすものと思われる。
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