Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications

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.