Table 2.
Overview of studies involving dental pulp stem cell secretome.
| Secretome Type | Administration | Preclinical Model | Factors Contained in Secretome | Results | Ref. |
|---|---|---|---|---|---|
| CM | - | Dorsal root ganglion neurons; Schwann cell | - | ↑ neurite outgrowth, Schwann cell viability and myelin formation | [54] |
| CM | - | PC12 cells | NGF, BDNF, GDNF and NT-3 | ↑ survival and neurite outgrowth | [55] |
| CM | - | SH-SY5Y cell line | - | ↑ neurite outgrowth, neuronal markers and voltage-gated Ca2+ channels | [56] |
| CM obtained by DPSC sheet | - | Neuronally differentiated SH-SY5Y neuroblastoma cells | BDNF, GDNF, NT-3 | ↑ formation and outgrowth of neurites | [57] |
| CM with and without B-27 supplement | - | Primary sensory neurons | Only with B-27: GDF-15, SCF R, Insulin; Only without B-27: FGF-4, GH, and VEGF-D; In common: NT-3, PDGF-AA, HGF, IGFBP (1–6), EGFR, OPG, VEGF, BMP-7, FGF-7, and IGF-1. |
↑ neurite outgrowth, B-27 supplement enhanced the effect | [58] |
| CM | - | Neural stem cells | - | ↑ neuritogenesis | [59] |
| CM | - | Primary trigeminal ganglion neuronal cells | NGF, BDNF, NT-3 and GDNF | ↑ survival, extensive neurite outgrowth and branching. | [60] |
| CM obtained by basal and G-CSF-mobilized DPSCs | - | TGW human neuroblastomacells | - | CM from mobilized DPSCs ↑ neurite extension | [61] |
| CM obtained by G-CSF-mobilized DPSCs | - | Neuronal Schwann RT4-D6P2T cells | - | ↑ proliferation and migratory activity | [62] |
| CM from SHEDs and DPSCs | - | Cerebral granular neurons with axon growth inhibitors | - | ↑ regeneration inhibiting axon growth inhibitors | [63] |
| CM from DPSCs, SCAPs and DFSCs | - | Preneuroblastic cell line IMR-32 cells | GCSF, IFN-γ, TGF-β, NGF, BDNF and NT-3 | ↑ neural differentiation. Neurite length was higher with DPSC CM. |
[64] |
| DPSC, BMSC and AMSC coculture | - | Retinal ganglion cells | NGF, BDNF, NT-3, VEGF, GDNF, PDGF-AA | ↑ survival. DPSCs released higher levels of NGF, BDNF and VEGF |
[65] |
| CM | - | Astrocytes exposed to OGD | - | ↑ protective effects. ↓ GFAP, nestin, and musashi-1 expression, ROS and IL-1β |
[66] |
| EXOs, CM or neuron–MSC-co-culture from DPSCs or BMSCs | - | Hippocampal cell line (H3) exposed to kainic acid | - | ↑ neuroprotection. CM fraction in the range 3–10 kDa showed neuroprotection | [67] |
| CM | - | Human neuroblastoma SH-SY5Y cells treated with A𝛽1–42 | VEGF, RANTES, FRACTALKINE, FLT-3, GM-CSF, MCP-1, neprilysin | ↓A𝛽 cytotoxicity and apoptosis. ↑ cell viability. DPSC secretome proteolytically degrade A𝛽1–42. |
[68] |
| CM | Intraperitoneally; early pre-symptomatic stage: at postnatal day 35–47; late pre-symptomatic stages: postnatal day 70–91; at symptom onset through to end-stage | Transgenic mice B6SJL-Tg (SOD1G93A)1 Gur/J | - | ↑ neuromuscular junction innervation; neuromuscular junction preservation, and motor neuron survival, lifespan | [69] |
| EXOs | Intravenous singular injection after reperfusion | C57BL/6 mice subjected to tMCAO injury followed by reperfusion.OGD/R induced BV2 cells | - | In vivo: ↓ brain oedema, cerebral infarction, neurological impairment and pro-inflammatory cytokines. In vitro: ↓ inflammation |
[70] |
| CM | Intrathecal injection 10 min before aSAH | Aneurysmal subarachnoid hemorrhage induced in Wistar rats | IGF-1, TGF-β, TIMP1, TIMP2 | ↑ oxygenation of injured brain, cognitive and motor function. ↓ neuroinflammation |
[71] |
| CM | Hindlimb skeletal muscles 8 weeks after streptozotocin injection | Sprague Dawley rats treated with Streptozotocin | - | ↑ sciatic motor/sensory nerve conduction velocity, sciatic nerve blood flow and intraepidermal nerve fiber density | [72] |
| CM | In the unilateral hindlimb skeletal muscles | Sprague Dawley rats treated with Streptozotocin | VEGF-C, BDNF, IL-1 β, IL-4, TLR4 and others |
↑ sciatic nerve conduction velocity, sciatic nerve blood flow. | [73] |
Aβ, amyloid β; aSAH, aneurysmal subarachnoid hemorrhage; AMSCs, adipose tissue derived MSCs; BDNF, brain-derived neurotrophic factor; BMP, bone morphogenetic protein; BMSCs, bone marrow MSCs; CM, conditioned medium; DFSCs, dental follicle stem cells; DPSCs, dental pulp stem cells; EXOs, exosomes; FGF, fibroblast growth factor; GDNF, glial-cell-derived neurotrophic factor; GFAP, glial fibrillary acidic protein; G-CSF, granulocyte colony-stimulating factor; HGF, hepatocyte growth factor; IFN, interferon; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor binding protein; IL, interleukin; MCP, Monocyte Chemoattractant Protein; MSCs, mesenchymal stem cells; NGF, nerve growth factor; NT, neurotrophin; OGD/R, oxygen-glucose deprivation–reperfusion; OPG, osteoprotegerin; PDGF, platelet-derived growth factor; ROS, reactive oxygen species; SCAPs, stem cells from apical papilla; SHEDs, stem cells from human exfoliated deciduous teeth; TGF, transforming growth factor; TIMP, tissue inhibitor of metalloproteinase; TLR, Toll like receptor; tMCAO, transient middle cerebral artery occlusion; VEGF, vascular endothelial growth factor; ↑, increase/improvements; ↓, reduction.