Development of a novel therapy based on stem cell conversion of dental pulp cells

Research Project

Project/Area Number	16K11600
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Prosthodontics/ Dental materials science and
Research Institution	The University of Tokushima
Principal Investigator	MIYAGI Mayu 徳島大学, 大学院医歯薬学研究部(歯学域), 助教 (20625719)
Co-Investigator(Kenkyū-buntansha)	井上美穂徳島大学, 大学院医歯薬学研究部(歯学域), 助教 (20271059) 松香芳三徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (90243477) 大野充昭岡山大学, 医歯薬学総合研究科, 准教授 (60613156)
Project Period (FY)	2016-04-01 – 2023-03-31
Project Status	Completed (Fiscal Year 2022)
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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	歯髄細胞 / TNF-α / 幹細胞 / 幹細胞化
Outline of Final Research Achievements	p38MAPK, TRAF1, and few others were detected in proteins obtained from TNF-α-stimulated dental pulp cells by antibody array. TNF-α stimulation did not affect cell proliferation or morphology of bone marrow-derived cells (BMC), but increased expression of undifferentiated marker genes. TNF-α-stimulated and non-stimulated BMC were cultured in their respective induction medium. The expression of marker genes were compared using RT-PCR. BMC expression of osteoblasts, chondrocytes, and neurons were higher in the non-stimulated group, while no significant difference was observed for adipocyte markers. Bone differentiation tended to be temporarily delayed by short-term TNF-α stimulation, suggesting that the proportion of cells with stem cell properties may have increased.
Academic Significance and Societal Importance of the Research Achievements	TNF-αがBMCの未分化性獲得に関与し、幹細胞性質を保ったまま大量培養できる可能性が示されたことから、歯槽骨や神経の再生、骨折・抜歯窩の治癒促進への貢献が期待される。また、メカニズムを解明し、歯髄組織において人為的に象牙芽細胞の再活性化を促すことで、歯髄組織の再生、象牙質の再生に結びつけることが可能となれば、抜髄リスクの軽減やう蝕の抑制、歯の延命、さらには、健康寿命の延長につながると考えている。また、この技術が他の細胞でも応用できれば、今後再生医療における細胞材料としての幅を広げることができると考える。