2021 Fiscal Year Final Research Report
Pathological analysis of periodontitis related Hypophosphatasia using human iPS cells and gene editing
| Project/Area Number |
19K19228
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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 57060:Surgical dentistry-related
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| Research Institution | Osaka University |
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Principal Investigator |
Nakano Chiho 大阪大学, 歯学研究科, 招へい教員 (30835856)
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| Project Period (FY) |
2020-02-01 – 2022-03-31
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| Keywords | iPS細胞 / 低ホスファターゼ症 / 組織非特異的アルカリホスファターゼ / セメント質形成不全 / 乳歯の早期脱落 / 象牙芽細胞分化誘導 / ゲノム編集 |
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| Outline of Final Research Achievements |
Hypophosphatasia is a rare inheritable disease characterized by defective bone mineralization. Early exfoliation of primary teeth is the most frequent abnormality in patients with HPP, but it is also reported other dental mineralized tissues, enamel and dentin, are affected.
In this study, we differentiated HPP patient-derived iPS cells into odontoblast-like cells. We examined a new method of odontogenic differentiation using human iPS cells. We generated human iPS cell-derived neural crest-like cells, which exhibited neural crest markers, then differentiated into odontoblast-like cells via mesenchymal stem cells. Odontoblast-like cells, which are derived iPS cells from three healthy adults, show characteristics of o dontoblasts. HPP patient-derived iPS cells show no mineralization after differentiation, while positive mineralization was recognized with the iPS cells corrected mutation causing HPP.
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| Free Research Field |
口腔外科学
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| Academic Significance and Societal Importance of the Research Achievements |
低ホスファターゼ症（HPP）は非常に稀な疾患で、乳歯の早期脱落はその主たる症状の一つとして知られる。他にも歯の形成不全など口腔内の症状が報告されているが、そのメカニズムは不明である。これらの口腔疾患の治療は歯の喪失を防ぐための予防が中心で、積極的な治療は存在しない。HPP患者の口腔疾患に対する理解を深めることが求められる。
本研究では健常人由来ヒトiPS細胞を用いて象牙芽細胞分化誘導を行い、その特徴を有する細胞を得ることに初めて成功した。またHPP患者由来疾患特異的ヒトiPS細胞を用いて象牙芽細胞石灰化不全の病態を再現し、今後のHPPにおける歯科的研究の足掛かりとなることができた。
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