| Project/Area Number |
19K19116
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57050:Prosthodontics-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 歯の再生 / iPS細胞 / 分化誘導 / 再生歯胚 / Organ-on-a-Chip / FGFR3 |
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| Outline of Research at the Start |
本研究はヒトiPS細胞の分化誘導実験において，細胞間相互作用の再現に適したツールであるOrgan-on-a-Chip技術を用いて，歯胚細胞の上皮-間葉相互作用を模倣し，歯胚への安定した分化誘導の実現を図る。
同目的を達成する為，ヒトiPS細胞由来の歯胚上皮・間葉系細胞をChip上で共培養し，歯胚形成と関連があるFGF3，FGF4，FGF10やBMP4を培地中に添加して分化誘導を促進させる。更に，申請者らが過去に樹立した，各種FGFをリガンドとするFGFR3のゲノム編集ヒトiPS細胞を，歯胚細胞へと分化させてChip上で同様に培養し，安定した分化誘導能を備えた歯の発生モデルChipの確立を試みる。
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| Outline of Final Research Achievements |
In this term for the research, the optimization of the method for human iPS cells (hiPSCs) differentiate towards the dental epithelial cells has performed. After hiPSCs were adapted in the feeder-free environment, cultured in the dental epithelial cell differentiation medium which contained the BMP-4 (BMP-4 had reported as the essential factor to form the tooth germ) and the Lithium Chloride (LiCl; Wnt/beta-Catenin signal activating factor).
I prepared the differentiation medium has been added such factors in several concentration manners and cultured the hiPSCs in different component medium. Finally, gene expression analysis of the cells has been conducted in some differentiation stages.
According that, the optimized condition has been discovered for hiPSC's dental epitherial differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果として，フィーダーフリー環境に馴化したヒト由来iPS細胞を対象とした，歯胚上皮細胞への分化誘導法の最適化に関する所見が得られた。同所見は，iPS細胞からエナメル芽細胞等，歯胚上皮系の細胞・組織を樹立する方法を確立する一助となり，発生学的な研究への応用や，齲蝕治療等において既存の手法を更に発展させる，技術革新に応用されることが期待できる。
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