Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair

Table 1

Examples for the beneficial of DPSCs on the central nervous system (CNS) diseases and the peripheral nervous system (PNS) diseases.

Type of diseases	Author	Differentiated status of DPSCs	Delivery method	Function of DPSCs	References
The central nervous system (CNS) diseases
Spinal cord injury (SCI)	Yamamoto et al.	Undifferentiated	DPSC transplantation	DPSCs inhibited massive SCI-induced apoptosis, preserved neural fibers and myelin, regenerated transected axons, and replaced damaged cells by differentiating into oligodendrocytes	[134]
	Yang et al.	Undifferentiated	DPSCs transplanted with cell pellets	DPSCs reduced inflammatory injury, promoted axonal regeneration, and reduced progressive hemorrhagic necrosis after SCI by inhibiting IL-1β, RhoA, and SUR1 expression	[136]
	Zhang et al.	Undifferentiated	DPSCs transplanted with chitosan-scaffold	DPSCs promoted motor functional recovery and inhibited cell apoptosis after SCI through secreting BDNF, GDNF, NT-3 and reducing the expression of active-caspase 3	[137]
Stroke	Song et al.	Undifferentiated	DPSCs cocultured with the conditioned medium in vitro	DPSCs conferred superior cytoprotection against cell death by reducing reactive gliosis and suppressing free radical and proinflammatory cytokine expression	[86]
	Song et al.	Undifferentiated	Intravenous DPSC injection	DPSCs reduced the infarct volume of SD rats after middle cerebral artery occlusion (MCAO) due to high angiogenesis and neurogenic differentiation and reduction of reactive gliosis	[87]
	Sugiyama et al.	Dental pulp-derived CD31(−)/CD146(−) side population (SP) stem cells	CD31(−)/CD146(−) SP cells transplantation	DPSCs promoted migration and differentiation of the endogenous neuronal progenitor cells and induced vasculogenesis and ameliorated ischemic brain injury of SD rats after transient middle cerebral artery occlusion (TMCAO)	[102]
	Yang et al.	Dental pulp-derived neuronal stem cells (tNSCs)	tNSC transplantation	Transplanted tNSC promoted function recovery after MCAO because of possessing hypoimmunogenic properties and immune modulation abilities	[142]
	Leong et al.	Undifferentiated	Intracerebral DPSC transplantation	DPSCs enhanced the recovery of poststroke sensorimotor deficits owing to differentiation into astrocytes and mediation through DPSC-dependent paracrine effects	[143]
Parkinson’s disease (PD)	Kanafi et al.	Dopaminergic cell-type differentiated	DPSCs were induced in vitro	DPSCs showed efficient propensity towards functional dopaminergic cell type	[65]
	Chun et al.	Dopaminergic neurons differentiated	DPSCs were treated with the dopaminergic neuron differentiation kit in vitro	DPSCs could differentiate into dopaminergic neural cells under experimental cell differentiation conditions	[69]
	Gnanasegaran et al.	Undifferentiated	Intrathecal DPSC transplantation into a mouse model of PD in vitro	DPSCs could treat the PD by regulating inflammatory mediators such as reducing the secretions of proinflammatory factors (IL-1α, IL-1β, IL6, IL8, and TNF-α) and upregulating the expression levels of anti-inflammatory factors (IL2, IL4, and TNF-β)	[146]
	Gnanasegaran et al.	DAergic-like cells differentiated	DPSCs were cultured in a system which consists of neuron and microglia in vitro	DPSCs were shown to have immunomodulatory capacities to reduce 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced deficits such as reactive oxygen species, DNA damages, and nitric oxide release	[147]
Alzheimer’s disease (AD)	Wang et al.	Undifferentiated	DPSCs cocultured with okadaic acid- (OA-) induced cellular model of AD in vitro	DPSC-treated cells had the morphology of restored neurons, elongated dendrites, densely arranged microfilaments, and thickened microtubular fibrils	[154]
	Ahmed et al.	Undifferentiated	DPSCs cocultured with amyloid beta (Aβ) peptide-induced cellular model of AD in vitro	DPSCs secreted and produced numerous vascular endothelial growth factor (VEGF), fractalkine, RANTES, fms-related tyrosine kinase 3 (FLT-3), and monocyte chemotactic protein 1 (MCP-1)	[155]
Retinal injury	Mead et al.	Undifferentiated	Intravitreal DPSC transplantation	DPSCs produced and secreted lots of neurotrophins in order to promote neuritogenesis/axogenesis of retinal cells	[83]
	Mead et al.	Undifferentiated	Intravitreal DPSC transplantation	DPSC provided protection from retinal ganglion cell (RGC) loss and retinal nerve fiber layer thickness (RNFL) thinning and preserved RGC function	[160]
	Bray et al.	Undifferentiated	DPSCs cocultured with the conditioned media which were obtained from organotypic explants from damaged rat retinas in vitro	DPSCs had ability to promote neurodifferentiation and expression of retinal neuronal markers in order to cure the rat retinas	[161]
The peripheral nervous system (PNS) diseases
Facial nerve defect	Sasaki et al.	Undifferentiated	DPSCs transplanted with poly-DL-lactide-coglycolide (PLGA) and collagen gel	DPSCs promoted the axon regeneration and myelinated nerve formation	[173]
Sciatic nerve defect	Sanen et al.	Schwann cell-type differentiated	DPSCs transplanted with NeuraWrap™ conduits	DPSCs promoted in growing neurites, myelinated nerve, and newly blood vessel formation and survival	[174]
Sciatic nerve defect	Askari et al.	Oligodendrocyte progenitor cell- (OPC-) type differentiated	DPSC-induced OPC transplantation	DPSCs could be differentiated into functional oligodendrocytes	[175]
Sciatic nerve defect	Omi et al.	Undifferentiated	DPSC transplantation	DPSCs increased the gene expression of interleukin-10 and promoted macrophages polarization towards anti-inflammatory M2 phenotypes	[176]