Table 1.
Potential of periodontal ligament stem cells in neural regeneration
| Cells | Induction | Effects | Delivery method | Target molecules | Type of study | Ref |
|---|---|---|---|---|---|---|
| PDLSCs | With bFGF + EGF | Differentiated to neuronal and glial cells patch clamp showed outward and inward currents | – | βIII-tubulin↑ nestin↑ GFAP+ synaptophysin + SOX1↑ NEFM↑ Noggin↓ | In vitro | [2] |
| PDLSCs | With bFGF and EGF | Differentiated to neural crest stem cells, glutamate‐induced calcium responses | – | βIII‐tubulin↑ NeuN↑ neurofilament↑ S100↑ neuron‐specific enolase↑ GFAP↑ miR‐132↑ ZEB2↓ | In vitro | [51] |
| Xeno‐free hPDLSCs | Differentiated to a very small and rounded cell body with thin neurite‐like projections | – | In vitro | [13, 64] | ||
| PDLSCs + GMSCs | With NGF | Several islands of dense structures, positive for neurogenic specific markers, candidates for nerve tissue engineering | Encapsulated in alginate/hyaluronic acid hydrogel | βIII-tubulin↑ GFAP+ VAMP2+ | In vitro | [57] |
| PDLSCs | Co-culturing PDLSCs with OA-induced SH-SY5Y cells | Recovery of cytoskeleton structure, cell shape and viability ↓apoptosis of okadaic acid‐induced SH‐SY5Y cells pTau | – | ↓apoptosis related molecules | In vitro | [59] |
| PDLSCs | ↓Inflammation and demyelination in the spinal cord in multiple sclerosis (MS) in animal model | Single-dose intravenous injection to the tail vein | ↓inflammation and demyelination molecules, neurotrophic factors↑ | In vivo | [60] | |
| DPSCs and PDLSCs | Migrate toward infracted areas and differentiate into neuron-like cells, in vivo in rat model of cerebral ischemia | Direct administration | ↓Notch pathway molecules ↑Wnt signaling pathway molecules Wnt3a↑ enolase ↑ tubulin↑ Thy-1↑ Jagged-1↓ | In vivo | [61] | |
| PDLSC-CM | PDLSCs obtained from RR-MS patients | Reduce inflammatory damage in the animal model of MS (in EAE mice) | Systemic administration | TGF‐β+IL‐10+ | In vivo | [62] |
| PDLCS-CM | under hypoxic conditions | Pathology‐independent ability of PDLSCs niche ↑functionality of the PI3K/Akt/mTOR axis modulate markers of oxidative stress, autophagy and apoptosis | Injection of vesicles or conditioned medium to MS animal model | ↓pro-inflammatory and ↑anti-inflammatory cytokines beclin‐1↑ LC3↑ Interferon‐γ↓ IL‐17↓BDNF↑ | In vitro in vivo | [62, 65, 66] |
| hPDLSCs-CM | Enhanced level of NFκB and TLR4 and decreased amount of IκB-α in lipopolysaccharide-stimulated NSC34 mouse motoneurons | – | ↑NFκB and TLR4 ↓IκB-α | In vitro | [67] | |
| PDLSCs | PDLSCs are in contact with retinal ganglion cells (RGCs) in retinal explant culture | Neuroprotective effect and enhanced neurite regeneration in retinal tissue without macrophage recruitment | – | BDNF↑ | In vitro | [68, 69] |
| PDLSCs | Electrically functional RGC survival and axonal regeneration in vivo in rat model of optic nerve injury | Intravitreal transplantation of PDLSCs | In vivo | [70] | ||
| PDLSCs | Differentiated into RGCs expression of ATOH7, POU4F2, β-III tubulin, MAP2, TAU, NEUROD1 and SIX3 formed synapses spontaneous electrical activities glutamate-induced calcium responses | – | VEGF↑ PTEN↑ | In vitro | [69] | |
| PDLSCs | Induction through chemically inhibiting Wnt and BMP signaling on Matrigel-coated surface | Differentiated into photoreceptor rosette-like outgrowth and excitatory glutamate response (Nrl+ rhodopsin+ Pax6+) | – | In vitro | [68, 71] | |
| PDLSCs | Erk1/2 signaling | Differentiated into Schwann cells | – | P75↑ S100↑ GFAP↑ P0↑ krox-20↑ Oct-6↑ | In vitro | [17, 77, 78] |
| PDLSCs | indirect co-culturing of heterogenous Schwann cells and PDLSCs (allogenic neurotrophic factors released by Schwann cells) | Presenting Schwann cell phenotype | – | In vitro | [75] | |
| PDLSCs | sandblasted and acid-etched (SA) titanium surface | Schwann-like cells highest expression of SC markers and proteins on the SA titanium surface | – | In vitro | [79] | |
| CM of the SCAPs, PDLSCs, and DPSCs | Induction of the cells with mixture of growth factors, Induction of SH-SY5Y cells with CM of the stimulated cells (in vitro) | BDNF↑ GDNF↑ in injured area, enhanced neurite outgrowth in SH-SY5Y cells in vitro, reduced the expression of caspase-3, higher level of neuronal markers in PDLSCs and SCAP, in rat sciatic nerve injury model | Transplantation of seeded fibrin glue conduits. Every fibrin glue conduit seeded with one of the stimulated cells and rat Schwann cells (rSC) | BDNF↑ GDNF↑ caspase-3↓ | In vivo | [41, 80] [82] |
| PDLSCs | Recovery of sensory function ↑myelinated axons and retrograde labeled sensory neurons crush-injured left mental nerve in rats | Injected into the crush-injured left mental nerve | ↑NGF receptor | In vivo | [80, 81] |