Restor Dent Endod.  2023 May;48(2):e20. 10.5395/rde.2023.48.e20.

Stem cell-derived exosomes for dentin-pulp complex regeneration: a mini-review

• Hammouda DA
• Mansour AM
• Saeed MA
• Zaher AR
• Grawish ME

• KMID: 2548223
• DOI: http://doi.org/10.5395/rde.2023.48.e20

Abstract

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023. The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogenactivated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp–like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.

Keyword

Dental pulp; Dental pulp capping; Dentin; Exosomes; Regenerative endodontics; Stem cells

Figure

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  Figure 1 Diagrammatic representation of (A) hemostasis, (B) early/late inflammatory, and (C) regenerative phases of pulp self-healing mechanisms.IL, interleukin; TGF-β1, transforming growth factor beta 1; PDGF, platelet-derived growth factor; DPSC, dental pulp stem cell.

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  Figure 2 Preferred reporting items for systematic reviews and meta-analyses flow diagram for article selection.

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  Figure 3 Schematic representation of exosome biogenesis and molecular cargo. Exosomes are formed through the inward budding of the endosomal membrane resulting in the formation of early endosomes, late endosomes, and multivesicular bodies (MVBs). Upon fusion of MVBs with the plasma membrane, exosomes are released into the extracellular space. The molecular cargo of exosomes consists of lipids, DNA, mRNA, microRNA, and proteins. On their surface, they carry the RNA ESCRT, Alix, Tsg101, and tetraspanins CD9, CD63, and CD81 markers. Parts of the figure were drawn using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).ESCRT, endosomal sorting complex required for transport.

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  Figure 4 Schematic representation of the suggested methods for the use of exosomes in dentin-pulp complex (DPC) regeneration. Parts of the figure were drawn using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).

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