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Differentiation of mouse-induced pluripotent stem cells into dental epithelial-like cells in the absence of added serum

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Abstract

Recent studies have successfully generated tooth-like structure by mimicking the reciprocal interaction between dental epithelial and mesenchymal cells in tooth organogenesis. However, clinical applications of these methods are limited primarily due to the lack of appropriate sources for dental epithelial cells. Induced pluripotent stem cells (iPSCs) are attractive as a source for dental epithelial cells due to their unique characteristics. In this study, we examined the effect of neurotrophin-4 (NT-4) on the differentiation of mouse iPSCs (miPSCs) into dental epithelial cells. Our results showed that the addition of NT-4 during the formation of embryoid body significantly triggered the upregulation of epithelial markers such as p63 and CK14, suggesting that NT-4 provides an inductive condition for the differentiation of miPSCs into epithelial cells. Expansion of the NT-4-treated cells under serum-free culture conditions improves the formation of cells with cobblestone-like morphology and significantly downregulated the expression of pluripotent and ectodermal markers. Phenotypic analysis revealed that a dental epithelial surface marker, CD49f, was highly expressed on these cells. Formation of miPSCs-derived dental epithelial-like cells was further confirmed by the expression of ameloblast-specific markers. These results suggest that the addition of NT-4 during the formation of embryoid body together with the serum-free culture condition promoted the differentiation of miPSCs into dental epithelial-like cells.

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Acknowledgements

This study was supported by Grant-in-Aid for Scientific Research (B) (No. 16H03182), Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

  1. Department of Biomaterials, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Aimi Naim Abdullah, Satoshi Miyauchi, Azusa Onishi & Koichi Kato

  2. Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Aimi Naim Abdullah, Azusa Onishi & Kotaro Tanimoto

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  1. Aimi Naim Abdullah
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  2. Satoshi Miyauchi
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  3. Azusa Onishi
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  4. Kotaro Tanimoto
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  5. Koichi Kato
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Correspondence to Koichi Kato.

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Editor: Tetsuji Okamoto

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Abdullah, A.N., Miyauchi, S., Onishi, A. et al. Differentiation of mouse-induced pluripotent stem cells into dental epithelial-like cells in the absence of added serum. In Vitro Cell.Dev.Biol.-Animal 55, 130–137 (2019). https://doi.org/10.1007/s11626-019-00320-z

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  • DOI: https://doi.org/10.1007/s11626-019-00320-z

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