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Review
. 2021 Jul 19;11(7):1858.
doi: 10.3390/nano11071858.

Periodontal and Dental Pulp Cell-Derived Small Extracellular Vesicles: A Review of the Current Status

Shu Hua  1 , Peter Mark Bartold  2 , Karan Gulati  2 , Corey Stephen Moran  2 , Sašo Ivanovski  1   2 , Pingping Han  1   2
Affiliations
Review

Periodontal and Dental Pulp Cell-Derived Small Extracellular Vesicles: A Review of the Current Status

Shu Hua et al. Nanomaterials (Basel). .

Abstract

Extracellular vesicles (EVs) are membrane-bound lipid particles that are secreted by all cell types and function as cell-to-cell communicators through their cargos of protein, nucleic acid, lipids, and metabolites, which are derived from their parent cells. There is limited information on the isolation and the emerging therapeutic role of periodontal and dental pulp cell-derived small EVs (sEVs, <200 nm, or exosome). In this review, we discuss the biogenesis of three EV subtypes (sEVs, microvesicles and apoptotic bodies) and the emerging role of sEVs from periodontal ligament (stem) cells, gingival fibroblasts (or gingival mesenchymal stem cells) and dental pulp cells, and their therapeutic potential in vitro and in vivo. A review of the relevant methodology found that precipitation-based kits and ultracentrifugation are the two most common methods to isolate periodontal (dental pulp) cell sEVs. Periodontal (and pulp) cell sEVs range in size, from 40 nm to 2 μm, due to a lack of standardized isolation protocols. Nevertheless, our review found that these EVs possess anti-inflammatory, osteo/odontogenic, angiogenic and immunomodulatory functions in vitro and in vivo, via reported EV cargos of EV-miRNAs, EV-circRNAs, EV-mRNAs and EV-lncRNAs. This review highlights the considerable therapeutic potential of periodontal and dental pulp cell-derived sEVs in various regenerative applications.

Keywords: cell-free therapy; exosomes; extracellular vesicles; nanomedicine; regeneration.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The biogenesis and contents of extracellular vesicles (EVs). (a) Biogenesis and size of three EV subtypes. (b) Common surface markers and cargos of EVs. sEVs: small extracellular vesicles; MVs: microvesicles; ApoBDs: apoptotic bodies; MVBs: multi-vesicular bodies; MHC: major histocompatibility complex; HSP: heat-shock protein; dsDNA: double-stranded DNA; miRNA: microRNA; circRNA: circular RNA.
Figure 2
Figure 2
Schematic showing the main cell population and cell products (EVs) within a healthy periodontium. Various cells reside in the periodontium, such as periodontal ligament (stem) cells (PDLSCs), fibroblasts (GFs) and stem cells (GMSCs) from the gingiva, osteoblasts (OBs), osteoclasts (OCs), and various immune cells. AB: alveolar bone; C: cementum; D: dentin; DP: dental pulp; PDL: periodontal ligament; SHED: dental pulp cells from human exfoliated deciduous teeth (SHED); SCAP: cells from periodontal apical papilla tissues (SCAP).
Figure 3
Figure 3
Various sEV isolation methods (a) and characterization methods (b) are used for periodontal (dental pulp) cells. UC: ultracentrifugation; NTA: nanoparticle tracking analysis; TEM: transmission electron microscopy; WB: Western blot; SEM: scanning electron microscopy; AFM: atomic force microscopy; BCA: bicinchoninic acid assay; DLS: dynamic light scattering; ELISA: enzyme-linked immunosorbent assay; confocal: confocal microscopy.
Figure 4
Figure 4
Summary of EV–miRNAs, circular RNAs (a,b) and proposed (c) function of periodontal cell-derived EV on recipient cells function. (a) Venn diagram showing no common EV–miRNAs found from PDL(S)Cs, GFs/GMSCs and DPSCs. (b) Listed EV–miRNAs and EV–circRNAs. (c) Proposed mechanism of how periodontal cell-derived EVs modulate inflammation, angiogenesis, osteo/odontogenesis via EV cargos, such as miRNA, mRNAs, lncRNAs, and circRNAs.
See this image and copyright information in PMC

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