| Project/Area Number |
17H04380
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Conservative dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
OKIJI Takashi 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (80204098)
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| Co-Investigator(Kenkyū-buntansha) |
勝部 憲一 東都大学, ヒューマンケア学部, 教授 (20233760)
大島 勇人 新潟大学, 医歯学系, 教授 (70251824)
金子 友厚 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (70345297)
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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 |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
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| Keywords | 歯髄組織再生 / 歯髄幹細胞 / 血管内皮細胞 / 歯学 / 歯内療法学 / 歯髄再生 / 歯内治療学 |
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| Outline of Final Research Achievements |
This study aimed (1) to elucidate cellular and molecular mechanisms involved in the dental pulp regeneration in a rat coronal pulp regeneration model using mesenchymal stem cell (MSC) implantation; and (2) to examine whether MSC-endothelial cell (EC) crosstalk participates in the accelerated pulp regeneration after MSC-EC co-implantation, using a co-culture system. mRNA and protein expression analysis of the regenerating pulp revealed M1-to-M2 transition of macrophages and reinnervation with nerve growth factor upregulation during the pulp regeneration process. LacZ-labeled cells were detected below the dentin bridge, suggesting differentiation of implanted MSCs into mineralized tissue-forming cells. The co-culture upregulated vascular endothelial cell growth factor secretion and mRNA expression of angiogenic factors and promoted tube formation in an NF-kB dependent manner, suggesting the NF-kB pathway plays a major role in the MSC-EC crosstalk-induced angiogenic responses.
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| Academic Significance and Societal Importance of the Research Achievements |
歯髄組織再生が可能となれば、天然歯の残存期間の飛躍的延長が期待される。本研究では、将来の臨床応用を見据え、独自のラット歯冠歯髄再生モデルを用いて歯髄組織再生過程で展開される細胞・分子機構の解明を図った結果、再生過程における幹細胞、マクロファージ、神経線維等の挙動を明らかにすることができた。さらに、幹細胞・血管内皮細胞混合移植で歯髄再生が促進されるとの申請者らの従来の知見に基づき、その機構をin vitro共培養系で解析し、両細胞間のクロストークによるNF-kB依存性の血管新生因子産生促進という新たな機構を見出した。以上の成果は、効率的な歯髄組織再生技法の創生に貢献しうると思われる
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