| Project/Area Number |
26293426
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Gifu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
石崎 明 岩手医科大学, 歯学部, 教授 (20356439)
川口 知子 (武田知子 / 川口 知子(武田知子)) 岐阜大学, 医学部附属病院, 医員 (30509815)
飯田 一規 岐阜大学, 大学院医学系研究科, 助教 (30585237)
畠山 大二郎 岐阜大学, 医学部附属病院, 講師 (60377653)
玉置 也剛 岐阜大学, 医学(系)研究科(研究院), 助教 (40585303)
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| Project Period (FY) |
2014-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | 再生医学 / 歯髄 / iPS細胞 / ヒト歯髄細胞 / 良質化 / ヒト歯髄 |
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| Outline of Final Research Achievements |
In this study, we examined the inductive efficiency and stability of iPS cells derived from human dental pulp cells. Our results were as follows; 1. Hypoxia condition improved the cell growth and establishing efficiency of primary culture. Furthermore, hypoxia condition was effective and useful for the stemness and high differential potency and could improve the efficiency of iPS cell induction and its quality. 2. Difference of DLX4 expression was observed between high and low inductive cell line to iPS cells. 3. DLX4 improved the inductive efficiency and quality of iPS cell colonies. Only DLX4 and Oct/Sox highly induced iPS cells as well as Oct/Sox, Klf4 and c-Myc. These findings suggested that DLX4 might play a replaceable role of Klf4 and c-Myc. 4. To reveal the DLX4 function engaging to TGFb signal pathway, we examined the induction under TGFb stimulation.TGFb stimulation significantly reduced the inductive efficiency and without the alternation of smad signal pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
iPS細胞の臨床応用において，遺伝子導入操作のや不均一性による「良いiPS細胞」とがん化にも繋がる「悪いiPS細胞」が大きな課題となっており「良質なiPS細胞を効率良く生み出す方策」が強く求められている。本研究では，iPS細胞の良質化・効率化を向上させる新たな因子DLX4を見出し，その機能解析を試みた。結果，DLX4が従来のKlf4, c-Mycに代替し良質なiPS細胞コロニーをもたらすこと，DLX4がTGFβシグナルに応答することより遺伝子操作に依らない細胞の外部刺激により細胞初期化を促進する可能性を見出した。また，研究に用いた歯髄幹細胞が再生医療資源として有用であることを示した。
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