Investigate the Odontogenic Differentiation and Dentin-Pulp Tissue Regeneration Potential of Neural Crest Cells

Maolin Zhang; Xiaochen Zhang; Jiaxin Luo; Ran Yan; Kunimichi Niibe; Hiroshi Egusa; Zhiyuan Zhang; Ming Xie; Xinquan Jiang

doi:10.3389/fbioe.2020.00475

Investigate the Odontogenic Differentiation and Dentin-Pulp Tissue Regeneration Potential of Neural Crest Cells

Front Bioeng Biotechnol. 2020 Jun 5:8:475. doi: 10.3389/fbioe.2020.00475. eCollection 2020.

Authors

Maolin Zhang^{1

2

3}, Xiaochen Zhang^{2

4}, Jiaxin Luo^{1

2}, Ran Yan^{1

2}, Kunimichi Niibe³, Hiroshi Egusa³, Zhiyuan Zhang^{2

4}, Ming Xie¹, Xinquan Jiang^{1

2}

Affiliations

¹ Department of Prosthodontics, School of Medicine, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
² Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China.
³ Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Japan.
⁴ Department of Oral and Maxillofacial-Head and Neck Oncology, School of Medicine, Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Stem cell-based developmental engineering has been considered as a promising strategy for tissue/organ regeneration. Tooth is formed by sequential reciprocal interactions between epithelium derived from surface ectoderm and mesenchymal cells derived from cranial neural crest. The neural crest cell is an appealing cell source for tooth development and regeneration research. In this study, we investigated the odontogenic differentiation and dentin-pulp complex regeneration potential of neural crest cells. Our results showed that neural crest cells (O9-1 mouse cranial neural crest cell line) can sequentially differentiate into dentin matrix acidic phosphoprotein 1 (DMP-1)-positive odontoblasts within a developing tooth germ in vitro. Moreover, O9-1 cells and induced pluripotent stem cell (iPSC)-derived neural crest-like cells (iNCLCs) can form well-organized vascularized dentin-pulp complex when transplanted in vivo with tooth scaffold. Furthermore, both O9-1 cells and iNCLCs can be differentiated into odontoblast-like cells, positive staining with odontogenic-related markers DMP-1 and dentin sialophosphoprotein (DSPP), under odontogenic induction with the administration of bone morphogenetic protein 4 (BMP-4). These results demonstrated that neural crest cells, especially the unlimited iNCLCs, are a promising cell source for tooth development and dental tissue/tooth organ regeneration studies.

Keywords: dentin–pulp complex regeneration; iPSC-derived neural crest-like cells; neural crest cells; odontogenic differentiation; tooth regeneration.