Table 1.
Overview of the main factors found in the dental MSC secretome.
| MSCs | Secretome | Contained Factors | Comparison with Other MSC Secretomes |
Ref. |
|---|---|---|---|---|
| SCAPs | CM | 2046 proteins, included chemokines, angiogenic, immunomodulatory, antiapoptotic, and neuroprotective factors, ECM proteins | 151 proteins were different by at least twofold compared to BMSCs. SCAPs CM: ↑ proteins involved in metabolic processes, transcription, chemokines and neurotrophins. ↓ proteins linked to biological adhesion, developmental processes, immune function, ECM and pro-angiogenic factors |
[31] |
| DPSCs | CM | Ang-2, EGF, Endoglin, Endothelin-1, Eotaxin-1, FGF-1, FGF-2, Flt-3L, Follistatin, G-CSF, GM-CSF, GRO pan, HB-EGF, HGF, IFNα2, IFNγ, IL-12(p40), IL-12(p70), IL-13, IL-15, IL-1B, IL-5, IL-8, IL-9, IP-10, Leptin, MCP-1, MCP-3, PDGF-AA, PDGF-BB, PLGF, RANTES, TGF-α, TGF-β1, TGF-β2, TGF-β3, TNFα, TNFβ, VEGF-A, VEGF-C, VEGF-D | Differences compared to UC-MSCs at different time points: Eotaxin-1, FGF-2, Fractalkine, GRO pan, IFNα2, IL-1α, IL-6, MCP-1, MCP-3, PDGF-BB, RANTES, TGF-β1, VEGF-A, VEGF-C | [32] |
| DPSCs | CM | IGF-1, IL10, IGFBP-6, NT-3, BMP-4, MIP-1δ, NAP-2, TGF-β3, TGF-β1, MIP-3α, TNF-α, TNF-β, ICAM-1, NT-4, I-TAC, TARC, Axl, THPO, TECK, Acrp-30, ICAM-3, EGFR, AgRP, XCL-1, MIF | Upregulated in DACCs: IGF-1, IL10, IGFBP-6 Downregulated in DACCs: NT-3, BMP-4, MIP-1δ, NAP-2, TGF-β3, TGF-β1, MIP-3α, TNF-α, TNF-β, ICAM-1, NT-4, I-TAC, TARC, Axl, THPO, TECK, Acrp-30, ICAM-3, EGFR, AgRP, XCL-1, MIF |
[34] |
| PDLSCs | CM | 99 proteins, including matrix proteins, enzymes, growth factors, cytokines, and angiogenic factors | - | [35] |
| DPSCs, SCAPs and DFSCs | CM | Osteogenic lineage related proteins were more in Dental MSC secretome | Dental MSCs showed more psteogenic protein compared to BMSCs | [36] |
| SHEDs | CM | FGF-2, IL-10, PDGF, SDF-1, Ang-1, TGF-β3, HGF, INF-γ, VEGF, and IL-6 | ↑ TGF-β3 and angiopoietin-1 in BMSCs, HGF and IFN-γ in SHED, VEGF in WJ-MSC. PDGF-A, IL-10, FGF-2, and SDF-1 were similar in all MSCs |
[37] |
| Permanent and deciduous-teeth PDLSCs | CM | 76 proteins in permanent-PDLSCs CM, 20 in deciduous-PDLSCs CM, and 19 in both samples; permanent-PDLSCs CM: proteins involved in cell growth, cell communication, and signal transduction, higher levels of NT-3 and NT-4 and angiogenesis-related cytokines such as EGF and IGF-1. Deciduous-PDLSCs CM: proteins involved in regulation of the cell cycle, cytokines involved in immune response and in tissue degradation and catalytic activities, including MMP1, PSMA1, and CUL7 |
- | [38] |
| GMSCs | EVs | Transcripts for growth factors such as TGF-β, FGF, VEGF, GDNF family ligands and neurotrophins, such as NGF, BDNF, NT-3 and NT-4, ILs and members of the Wnt family | - | [41] |
| PDLSCs | EVs | Contained non-coding RNA: antisense RNA, long non-coding RNA, miRNAs (MIR24-2, MIR142, MIR335, MIR490, and MIR296) | - | [42] |
| SCAPs | EXOs | 593 piRNAs | 920 piRNAs in BMSC-EXOs. 21 piRNAs were differentially expressed |
[43] |
| DPSCs | CM | CM obtained in normoxic conditions: ↑ molecules with anti-inflammatory, tissue repair and regenerative properties compared to hypoxic CM | - | [44] |
| SHEDs, young DPSCs, old DPSCs | CM | IL-4, IL-2, CXCL10, IL-1B, TNF-A, CCL2, IL-17A, IL-6, IL-10, IFN-γ, IL-12P17, CXCL8, TGF-β1, ANG-2, EGF, EPO, BFGF, G-CSF, GM-CSF, HGF, M-CSF, PDGF-AA, PDGF-BB, SCF, TGF-α, VEGF SHEDs and young DPSCs: ↑ growth factors, ↓ pro-inflammatory cytokines |
- | [47] |
| DPSCs treated with THSG | CM | Treatment increased: AKT2, persephin, NGFR, PTHrP, maspin, leptin, STAT3, YES1, MMP-13, FGF-5, HER3, FGF-16, IGF-BP1, LH, myostatin, HDAC1, SDF-1β, MDC, MCP-4, L-selectin, TNF-α, STAT6, β-2-MICROGLOBULIN, APRIL, eotaxin-3, MCP-1, LIGHT, galectin 3, LD78β, MIP-1β, granzyme B, LEC. Treatment reduced: TSH, EGF, CTGFL, HGH, FSH, vaspin, PDGF-AA, GM-CSF, KGF, FGF-acidic, FAK, GDF-3, TGF-β2, IGF-I, MMP-2, STAT-1, TIMP-1, eotaxin, MMP-23, IL-12, galectin-1, ena-78, IL-15, IL-4, IL-22, IL-6, IL-13, IL-1β |
- | [49] |
| FGF-2-modified GMSCs | CM | ↑ VEGF-A, FGF-2, TGF-β. | - | [50] |
| SHEDs treated with Ascorbic acid | CM | Treatment ↑ VEGF, TGF-α, SCF, TGF-β, IGF-1, HGF, bFGF, Ang-1, EGF, Ang-2, TNF-α, IL-10, IL-6, IL-17A, NO, IDO, SDF-1, PGE-2. Treatment ↓ CCL2, TGF-β1 |
- | [51] |
| Undifferentiated PDLSCs or PDLSCs exposed to osteogenic differentiation medium | EVs | 69–557 circRNAs and 2907–11,581 lncRNAs. After 5 and 7 days of exposure to differentiation medium: ↑ 3 circRNAs and 2 lncRNAs, ↓ 39 circRNAs and 5 lncRNAs | - | [52] |
| Undifferentiated PDLSCs or osteogenic differentiated PDLSCs | EXOS | 72 upregulated miRNAs, 35 downregulated miRNAs after osteogenic induction | - | [53] |
Ang, angiopoietin; BDNF, brain-derived neurotrophic factor; BMP, bone morphogenetic protein; BMSCs, bone marrow MSCs; circRNA, circular RNA; CM, conditioned medium; CUL7, cullin 7; CXCL, C-X-C motif chemokine ligand; DACCs, developing apical complex cells; DFSCs, dental follicle stem cells; DPSCs, dental pulp stem cells; ECM, extracellular matrix; EGF, epidermal growth factor; ECM, extracellular matrix; EVs, extracellular vesicles; EXOs, exosomes; FGF, fibroblast growth factor; G-CSF, granulocyte colony-stimulating factor; GDNF, glial-cell-derived neurotrophic factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GMSCs, gingival MSCs; HGF, hepatocyte growth factor; ICAM, Intercellular Adhesion Molecule; IDO, indoleamine 2,3-dioxygenase; IFN, interferon; IGF, insulin-like growth factor; IL, interleuchin; lncRNA, long noncoding RNA; MCP, Monocyte Chemoattractant Protein; miRNA, microRNA; MMP, matrix metalloproteinase; NGF, nerve growth factor; NT, neurotrophin; PDGF, platelet-derived growth factor; PDLSCs, periodontal ligament stem cells; piRNA, PIWI-interacting RNAs; PSMA1, Proteasome subunit, alpha type; SCAPs, stem cells from apical papilla; SDF, stromal cell–derived factor; SHEDs, stem cells from human exfoliated deciduous teeth; TGF, transforming growth factor; THSG, 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside; TIMP, tissue inhibitor of metalloproteinase; TNF, Tumor Necrosis Factor; UC-MSCs, umbilical cord mesenchymal stem cells; VEGF, vascular endothelial growth factor ↑, increase/improvements; ↓, reduction.