| Project/Area Number |
18K09641
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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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| Review Section |
Basic Section 57040:Regenerative dentistry and dental engineering-related
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
IRIE Kazuharu 北海道医療大学, 歯学部, 教授 (70223352)
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| Co-Investigator(Kenkyū-buntansha) |
吉羽 邦彦 新潟大学, 医歯学系, 教授 (30220718)
建部 廣明 北海道医療大学, 歯学部, 講師 (40638293)
細矢 明宏 北海道医療大学, 歯学部, 教授 (70350824)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Gli1 / 歯髄幹細胞 / 象牙芽細胞 / フェイトマッピング解析 / 幹細胞 / 硬組織 / CD146 / 象牙質 / 歯槽骨 / 歯髄 / 硬組織形成 / 歯根膜 / 象牙質再生 / フェイトマッピング |
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| Outline of Final Research Achievements |
Fate mapping analysis with an inducible Cre / loxP system was performed to investigate the process of differentiation from Gli1-positive dental pulp stem cells into hard tissue-forming cells and odontoblasts. After administration of tamoxiphen to 4-week-old mice, the first molar tooth was removed and transplanted into the litter, and Tomato-labeled cells were arranged on the surface of the hard tissue formed in the pulp, and Gli1-positive cells were intradentally. It was shown that it had differentiated into hard tissue-forming cells. It was confirmed that these Gli1-positive cells can form colonies and differentiate into chondrocytes, osteoblasts, and adipocytes, and have stem cell characteristics. Furthermore, it was suggested that these cells may be CD146 positive in the dental papilla and pulp in the early stage of dentin formation. It was confirmed that it has stem cell characteristics.
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| Academic Significance and Societal Importance of the Research Achievements |
生体親和性のある再生医療を達成するためには、in vivoにおける発生生物学的知見や組織構築に基づいたアプローチが必要である。今回Gli1陽性歯髄幹細胞が硬組織を形成する細胞に分化することを明らかにしたこと、またこの分化過程にCD146やα-SMA陽性の血管周囲の細胞が関わっていることを明らかにしたにより、今後、この細胞の各分化段階における遺伝子発現等を解析することにより、幹細胞から象牙芽細胞に分化する際に重要な転写調節因子を発見できるのみならず、歯髄の組織幹細胞の維持に関する転写調節遺伝子群や増殖・分化制御に関連するサイトカインや細胞外基質との関連が明らかにする道筋が示された。
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