Theranostics 2020; 10(16):7409-7421. doi:10.7150/thno.44782 This issue Cite

Research Paper

Therapeutic potential of HERS spheroids in tooth regeneration

Yufeng Duan1,2,3,4*, Xuebing Li1,2,3,4*, Sicheng Zhang1,2,3,4*, Shikai Wang1,2,3,4, Tao Wang1,2,3,4, Hong Chen1,2,3,4, Yan Yang1,2,3,4, Sixun Jia1,2,3,4, Guoqing Chen2,5✉, Weidong Tian1,2,3,4✉

1. State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
2. National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
3. National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
4. Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
5. School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
*These authors contributed equally.

Citation:
Duan Y, Li X, Zhang S, Wang S, Wang T, Chen H, Yang Y, Jia S, Chen G, Tian W. Therapeutic potential of HERS spheroids in tooth regeneration. Theranostics 2020; 10(16):7409-7421. doi:10.7150/thno.44782. https://www.thno.org/v10p7409.htm
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Abstract

Graphic abstract

Hertwig's epithelial root sheath (HERS) plays indispensable roles in tooth root development, including controlling the shape and number of roots, dentin formation, and helping generate the cementum. Based on these characteristics, HERS cell is a potential seed cell type for tooth-related tissue regeneration. However, the application is severely limited by a lack of appropriate culture methods and small cell numbers.

Methods: Here, we constructed a 3D culture method to expand functional HERS cells into spheroids, and investigated characteristics and application of dental tissue regeneration of these spheroids. HERS spheroids and HERS cells (2D monolayer culture) were compared in terms of biological characteristics (such as proliferation, self-renewal capacity, and stemness) in vitro and functions (including differentiation potential and inductive ability of dentin formation) both in vitro and in vivo. Further, transcriptome analysis was utilized to reveal the molecular mechanisms of their obvious differences.

Results: HERS spheroids showed obvious superiority in biological characteristics and functions compared to 2D monolayers of HERS cells in vitro. In vivo, HERS spheroids generated more mineralized tissue; when combined with dental papilla cells (DPCs), HERS spheroids contributed to dentin-like tissue formation. Moreover, the generation and expansion of HERS spheroids rely to some degree on the HIF-1 pathway.

Conclusion: HERS spheroid generation is beneficial for functional HERS cell expansion and can provide a useful cell source for further tooth regeneration and mechanistic research. Notably, HIF-1 pathway plays a critical role in HERS spheroid formation and function.

Keywords: Hertwig's epithelial root sheath (HERS), 3D culture, spheroid, HIF-1 pathway, tissue regeneration


Citation styles

APA
Duan, Y., Li, X., Zhang, S., Wang, S., Wang, T., Chen, H., Yang, Y., Jia, S., Chen, G., Tian, W. (2020). Therapeutic potential of HERS spheroids in tooth regeneration. Theranostics, 10(16), 7409-7421. https://doi.org/10.7150/thno.44782.

ACS
Duan, Y.; Li, X.; Zhang, S.; Wang, S.; Wang, T.; Chen, H.; Yang, Y.; Jia, S.; Chen, G.; Tian, W. Therapeutic potential of HERS spheroids in tooth regeneration. Theranostics 2020, 10 (16), 7409-7421. DOI: 10.7150/thno.44782.

NLM
Duan Y, Li X, Zhang S, Wang S, Wang T, Chen H, Yang Y, Jia S, Chen G, Tian W. Therapeutic potential of HERS spheroids in tooth regeneration. Theranostics 2020; 10(16):7409-7421. doi:10.7150/thno.44782. https://www.thno.org/v10p7409.htm

CSE
Duan Y, Li X, Zhang S, Wang S, Wang T, Chen H, Yang Y, Jia S, Chen G, Tian W. 2020. Therapeutic potential of HERS spheroids in tooth regeneration. Theranostics. 10(16):7409-7421.

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