Regeneration of dentin-pulp complex from iPS cells using new odontoblasts differentiation mechanism and polarity regulation
| Project/Area Number |
18H02984
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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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| Review Section |
Basic Section 57040:Regenerative dentistry and dental engineering-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大津 圭史 岩手医科大学, 歯学部, 准教授 (60509066)
横山 拓矢 岩手医科大学, 医学部, 講師 (70772094)
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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 |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
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| Keywords | iPS細胞 / 再生 / 象牙芽細胞 / 象牙質歯髄複合体 / iPS / 歯髄再生 / Semaphorin4D / Copine-7 / 象牙質再生 / ヒトiPS細胞 / 極性制御 / CPNE7 / iPSC / Semaphorin / 象牙芽細胞分化 / 歯の再生 / ３Dオルガノイド / 神経堤細胞 / 象牙質歯髄複合体再生 / 細胞極性制御 |
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| Outline of Final Research Achievements |
The aim of this study was to develop a technology to induce dentin-pulp complex formation from human iPS cells (hiPS) by using human Copine-7 (hCPNE7) and Semaphorin4D, which regulates cell polarity. MSCs) induced from hiPS and miPS cells were differentiated into odontoblasts when exposed to hCPNE7 or hCPNE7-expressing HAT7 (rat enamel blast cell line) culture supernatant. Furthermore, the basement membrane component secreted by the newly established Hertwig epithelial sheath cell line (HERS02T) also showed high induction of odontblast differentiation and polarity toward mouse incisor papillary mesenchymal stem cells, and similar results were obtained for NCLCs. The combined 3D culture of epithelial cell organoids and NCLC organoids showed enhanced differentiation induction and calcification formation.
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| Academic Significance and Societal Importance of the Research Achievements |
歯髄は疎性結合組織でできており，歯の感覚や防御機構を担っている。この歯髄に感染が及んだ場合は抜髄（歯髄除去）が必要となるが，除去された歯髄腔内は人工的材料で充填するのみである。そのため象牙質の知覚や修復能は失われ，歯自体も脆弱になる。歯髄の再生に関する研究は，不用となった歯の間葉系幹細胞を用いた再生が臨床トライアルまで来たが，具体的な実績にはなっていない。本研究の成果によってiPS細胞を利用することで生体から細胞を採取するリスクもなくなり，より現実味が帯びてきたと言える。iPS細胞を使った再生医療は他の器官を含めて本質的課題が多く残るが，将来的な医療としての基礎データを提示できた。
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Report
(5 results)
Research Products
(40 results)
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[Journal Article] Loss of Stemness, EMT, and Supernumerary Tooth Formation in Cebpb-/-Runx2+/- Murine Incisors.2018
Author(s)
Saito K, Takahashi K, Huang B, Asahara M, Kiso H, Togo Y, Tsukamoto H, Mishima S, Nagata M, Iida M, Tokita Y, Asai M, Shimizu A, Komori T, Harada H, MacDougall M, Sugai M, Bessho K.
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 5169-5169
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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