Dental Tissue-Derived Human Mesenchymal Stem Cells and Their Potential in Therapeutic Application

Table 1

Preclinical studies on treatment of dental diseases based on dental MSCs.

Disease target	Type of dental MSCs or their secretions	Animal model	Experiment design			Time	Results or outcome		Reference
			Cell density Administration	Biomaterials/scaffolds	Growth factors		Tissue regeneration	Effect evaluation and safety assessment
Endodontic diseases	hDPSCs	Nude mice	Subcutaneous; transplantation	Human treated dentin (hTD)	—	4, 6, and 8 weeks	Dentin-like tissue	IHE: DSPP, DMP1, and human mitochondria antibodies	[70]
	hDPSCs	Nude mice	Subcutaneous injection 100 μL	Nanofibrous spongy microspheres (NF-SMS)	Odontogenic medium	6 weeks	Dentin-like tissue	IHE: DSPP; Safety: NF-SMS almost completely degraded	[71]
	hDPSCs modified by PDGF-BB	Mice	—; Subcutaneous transplantation	Porous CPC scaffolds	—	12 weeks	Dentin-pulp complex	Positive markers in IHE: DSPP and PDGF-BB protein secreted endogenous stem/progenitor cell homing	[72]
	Canine DPSCs	Beagle dogs; Pulpotomy	Autologous transplantation	Absorbable gelatin sponge	Simvastatin (SIM)	10 weeks	Coronal pulp	RGE: closure of the root apex and thickening of the root canal wall; HE: regenerated pulp filling in nearly the entire pulp cavity with odontoblastic cells	[75]
	Porcine DPSCs	Minipigs; Pulpectomy	Autologous transplantation; Pulp chamber	Injectable nanopeptide hydrogel	—	21 days	Failed; No pulp	Micro-CT: reparative mineralized bridge in the residual pulp; failure of partial pulp regeneration	[76]
	Swine DPSCs	Miniswine	Autologous/allogeneic transplantation; Root canal	Injectable hyaluronic acid (HyA) gel or collagen TE gel	—	3~5 months	Dentin-like; pulp-like	IHE: DSPP, DMP1, BSP, and Nestin; HE: regeneration of vascularized pulp-like tissue with a layer of newly deposited dentin-like tissue or osteodentin along the canal walls.; Safety: no overcalcification of the pulp canal space after 5 months of follow-up	[71]
	Canine mobilized DPSCs	Dogs	Autologous transplantation; Root canal	Drug-approved collagen	Granulocyte colony-stimulating factor; (G-CSF)	14~180 days	Functional dental pulp	HE: regenerative pulp with well vasculature and innervation on day 14; RG: complete obliteration of the enlarged apical portion and lateral and coronal dentin formation; Laser Doppler: functional recovery of pulpal blood flow after 90 days; Pulp vitality: positive response on day 180; Safety: no adverse effects on both the whole and local	[77]
	Pig DPSCs	Minipig	DPSC aggregates; Autologous transplantation; Root canals	—	—	3 months	Whole pulp tissue	HE: regenerated pulp tissue containing an odontoblast layer and blood vessels; IHE: NeuN	[79]
Periodontal diseases	Human SCAPs	Minipig	Local injection; Periodontal defect	—	—	12 weeks	Periodontal tissue	Clinical assessments: PD, GR, and AL loss values decrease; CT scan: alveolar bone regeneration; HE: remarkable regeneration of periodontal tissues (Sharpey’s fibers, periodontal ligament, and cementum)	[84]
	Human PDLSC-CM	Rat	Transplantation; Periodontal defect	Collagen sponge	—	4 weeks	Periodontal tissue	Micro-CT: alveolar bone regeneration, decreased exposed root surface area; HE: new periodontal tissue formation, dense fibrous connective tissues, periodontal ligament, osteoblast-like cells, small islet-like bone clusters, more united crestal bone	[103]
	SFRP2-human SCAPs	Miniature pig	Local injection; Periodontal defect	—	—	12 weeks	Periodontal tissue	Clinical assignment: values of probing depth, gingival recession, and attachment loss; Micro-CT: alveolar bone regeneration; HE: increased tissue regeneration (increased height of newborn alveolar bone, and mature and thicker new cementum, periodontal ligament, and Sharpey’s fibers)	[85]
	Human PDLSCs	Rat	PDLSC-amnion	Amnion	—	4 weeks	Periodontal tissue	Micro-CT images: new bone formation; HE: cementum-like, narrow connective tissues, PDL-like tissues	[86]
	Human GMSC-CM	Rat	Transplantation	Collage membrane	—	1, 2, and 4 weeks	Periodontal tissue	HE: newly formed periodontal tissue; IHE: TNF-α, IL-1β, IL-10, BSP-II, and Runx2	[87]

DSPP: dentin sialophosphoprotein; DMP1: dentin matrix protein 1; HE: hematoxylin and eosin; IHE: immunohistochemical stains; PDGF: platelet-derived growth factor; RG: radiographic examination; BSP: bone sialoprotein; DAPI: 4,6-diamidino-2-phenylindole; PD: probing depth; GR: gingival recession; AL: attachment loss; CM: conditioned medium; SFRPs: secreted frizzled-related proteins; Amnion: decellularized amniotic membrane.