Theranostics 2020; 10(13):5914-5931. doi:10.7150/thno.43156 This issue Cite

Research Paper

Exosome-like vesicles derived from Hertwig's epithelial root sheath cells promote the regeneration of dentin-pulp tissue

Sicheng Zhang1,2,3,4#, Yan Yang1,2,3,4#, Sixun Jia1,2,3,4, Hong Chen1,2,3,4, Yufeng Duan1,2,3,4, Xuebing Li1,2,3,4, Shikai Wang1,2,3,4, Tao Wang1,2,3,4, Yun Lyu2,5, 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.
#: Sicheng Zhang and Yan Yang contributed equally to this work.

Citation:
Zhang S, Yang Y, Jia S, Chen H, Duan Y, Li X, Wang S, Wang T, Lyu Y, Chen G, Tian W. Exosome-like vesicles derived from Hertwig's epithelial root sheath cells promote the regeneration of dentin-pulp tissue. Theranostics 2020; 10(13):5914-5931. doi:10.7150/thno.43156. https://www.thno.org/v10p5914.htm
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Abstract

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Background: The formation of dentin-pulp involves complex epithelial-mesenchymal interactions between Hertwig's epithelial root sheath cells (HERS) and dental papilla cells (DPCs). Earlier studies have identified some of the regulatory molecules participating in the crosstalk between HERS and DPCs and the formation of dentin-pulp. In the present study we focused on the role of HERS-secreted exosomes in DPCs and the formation of dentin-pulp. Specifically, we hypothesized that exosome-like vesicles (ELVs) might mediate the function of HERS and trigger lineage-specific differentiation of dental mesenchymal cells. To test our hypothesis, we evaluated the potential of ELVs derived from a HERS cell line (ELVs-H1) in inducing in vitro and in vivo differentiation of DPCs.

Methods: ELVs-H1 were characterized using transmission electron microscopy and dynamic light scattering. The proliferation, migration, and odontoblast differentiation of DPCs after treatment with ELVs-H1, was detected by CCK8, transwell, ALP, and mineralization assays, respectively. Real time PCR and western blotting were used to detect gene and protein expression. For in vivo studies, DPC cells were mixed with collagen gel combined with or without ELVs and transplanted into the renal capsule of rats or subcutaneously into nude mice. HE staining and immunostaining were used to verify the regeneration of dentin-pulp and expression of odontoblast differentiation markers.

Results: ELVs-H1 promoted the migration and proliferation of DPCs and also induced odontogenic differentiation and activation of Wnt/β-catenin signaling. ELVs-H1 also contributed to tube formation and neural differentiation in vitro. In addition, ELVs-H1 attached to the collagen gel, and were slowly released and endocytosed by DPCs, enhancing cell survival. ELVs-H1 together with DPCs triggered regeneration of dental pulp-dentin like tissue comprised of hard (reparative dentin-like tissue) and soft (blood vessels and neurons) tissue, in an in vivo tooth root slice model.

Conclusion: Our data highlighted the potential of ELVs-H1 as biomimetic tools in providing a microenvironment for specific differentiation of dental mesenchymal stem cells. From a developmental perspective, these vesicles might be considered as novel mediators facilitating the epithelial-mesenchymal crosstalk. Their instructive potency might be exploited for the regeneration of dental pulp-dentin tissues.

Keywords: epithelial-mesenchymal interaction, Hertwig's epithelial root sheath cell, exosome-like vesicle, odontogenic differentiation, pulp-dentin regeneration.


Citation styles

APA
Zhang, S., Yang, Y., Jia, S., Chen, H., Duan, Y., Li, X., Wang, S., Wang, T., Lyu, Y., Chen, G., Tian, W. (2020). Exosome-like vesicles derived from Hertwig's epithelial root sheath cells promote the regeneration of dentin-pulp tissue. Theranostics, 10(13), 5914-5931. https://doi.org/10.7150/thno.43156.

ACS
Zhang, S.; Yang, Y.; Jia, S.; Chen, H.; Duan, Y.; Li, X.; Wang, S.; Wang, T.; Lyu, Y.; Chen, G.; Tian, W. Exosome-like vesicles derived from Hertwig's epithelial root sheath cells promote the regeneration of dentin-pulp tissue. Theranostics 2020, 10 (13), 5914-5931. DOI: 10.7150/thno.43156.

NLM
Zhang S, Yang Y, Jia S, Chen H, Duan Y, Li X, Wang S, Wang T, Lyu Y, Chen G, Tian W. Exosome-like vesicles derived from Hertwig's epithelial root sheath cells promote the regeneration of dentin-pulp tissue. Theranostics 2020; 10(13):5914-5931. doi:10.7150/thno.43156. https://www.thno.org/v10p5914.htm

CSE
Zhang S, Yang Y, Jia S, Chen H, Duan Y, Li X, Wang S, Wang T, Lyu Y, Chen G, Tian W. 2020. Exosome-like vesicles derived from Hertwig's epithelial root sheath cells promote the regeneration of dentin-pulp tissue. Theranostics. 10(13):5914-5931.

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