Table 1 Potential of periodontal ligament stem cells in neural regeneration

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]