Table 3.
Summary of the included studies investigating the effect of dental MSCs' secretome/conditioned medium on dental and periodontal tissue regeneration.
| Authors, year | Cell origin-contributing factor | Scaffold | Study model | Factors contained in dental MSC-CM | Factors promoted by dental MSC-CM | Outcome |
|---|---|---|---|---|---|---|
| Dental tissue regeneration | ||||||
| SHED-CM | ||||||
| de Cara et al., 2019 [123] | Human SHED-CM | - | In vivo orthotropic model of dental pulp regeneration in rats. In vitro |
- | VEGF-A &↓ 7AAD | Stimulated angiogenesis, formation of connective tissue similar to dental pulp, and reduced apoptosis. |
| Dental pulp MSC-CM | ||||||
| Iohara et al., 2008 [158] | Porcine dental pulp MSC-CM | - | In vitro | - | MMP3, VEGF-A, GM-CSF, & G-CSF. | Promoted macrovascular proliferation of HUVECs and inhibited its apoptosis. |
| Bronckaers et al., 2013 [138] | Human dental pulp MSC-CM | - | In vitro | VEGF, IL-8, MCP-1, uPA, TIMP-1, PAI-1, IGFBP-3, & endostatin. | FGF-2 | Enhanced endothelial cell migration and blood vessels formation. |
| Hayashi et al., 2015 [107] | Porcine dental pulp MSC-CM | Root with collagen. | In vivo ectopic tooth transplantation mouse model. | TRH-DE mRNA. | Syndecan 3, TRH-DE, CXCL14, G-CSF, BDNF, NPY, IL-1α, IL-6, IL-8, IL-16, and MCP-1. | Promoted odontoblastic migration, proliferation, differentiation, and neovascularization. |
| Murakami et al., 2015 [62] | Dog dental pulp MSC-CM | - | In vitro pulp disease. | - | DSPP & enamelysin. | Induced dental pulp MSC proliferation, migration, and odontoblastic differentiation. Stimulated HUVECs angiogenesis. |
| Huang et al., 2016 [155] | Human dental pulp MSC-EXs | Type I collagen membranes and root slice. Collagen sponges. |
In vivo ectopic tooth transplantation. In vitro |
- | BMP2, BMP9, TGF-β, PDGF, RUNX2, & DSPP. | Stimulated dental pulp MSCs odontoblastic differentiation. |
| Kawamura et al., 2016 [156] | Porcine dental pulp MSC-CM | Root - |
In vivo ectopic tooth transplantation mouse model. In vitro pulp disease. |
- | TRH-DE, enamelysin, PLAP-1, & periostin. Vascular endothelial cadherin. |
Promoted myoblasts proliferation, migration, and odontoblastic differentiation in the presence of EDTA. Stimulated HUVECs angiogenesis. |
| Nakayama et al., 2017 [157] | Human dental pulp MSC-CM | - | In vitro | - | ↓ caspase-3 | Mobilized dental pulp MSC-CM promoted fibroblast proliferation and migration, and inhibited its apoptosis. |
| Periodontal tissue regeneration | ||||||
| Periodontal ligament MSC-CM | ||||||
| Nagata et al., 2017 [181] | Human periodontal ligament MSC-CM | - | In vivo rat with periodontal defect | TIMP1, uPA, VEGF, IGFBP6, IGFBP2, PDGF-β, collagen, fibronectin & less amount of Serpin E1, MCP-1. | ↓ TNF-α, IL-6, IL-1β, & COX-2. | Promoted new tissue formation and periodontal tissue healing. |
BDNF: brain-derived neurotrophic factor; BMP: bone morphogenetic protein; CM: conditioned medium; COX-2: cyclooxygenase-2; CXCL14: chemokine (C-X-C motif) ligand 14; DSPP: dentin sialophosphoprotein; EXs: exosomes; FGF: fibroblast growth factor; G-CSF: granulocyte colony-stimulating factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; HUVECs: human umbilical vascular endothelial cells; IGFBP: insulin-like growth factor-binding protein; IL: interleukin; MCP-1: monocyte chemoattractant protein-1; MMP: matrix metalloproteinase; mRNA: messenger RNA; MSCs: mesenchymal stem cells; NPY: neuropeptide Y; PAI-1: plasminogen activator inhibitor-1; PDGF: platelet-derived growth factor; PLAP-1: periodontal ligament-associated protein 1; RUNX2: runt-related transcription factor 2; Serpin E1: serine protease inhibitor E1; SHED: stem cells derived from human exfoliated deciduous teeth; TGF-β: transforming growth factor-β; TIMP-1: tissue inhibitor of metalloproteinase-1; TNF-α: tumor necrosis factor alpha; TRH-DE: thyrotropin-releasing hormone degrading enzyme; uPA: urokinase plasminogen activator; VEGF: vascular endothelial growth factor.