Neural crest-derived mesenchymal stem cells: Fates and perspectives

Table 1 Dental stem cell-based clinical trials registered at ClinicalTrials.gov

Registration ID	Status	Diseases	Study design	Cell source	Administration route	Number of patients	Interventions		Follow-up period	Phase	Outcomes	Ref.
							Test group	Control group
NCT06097780	Not yet recruiting	Huntington’s disease	Randomized; parallel assignment; single-blind (outcomes assessor)	Dental pulp	Intravenous administrations	120	Intravenous human DPSCs administrations	Intravenous placebo administrations	1 year	Phase 3
NCT05924373	Recruiting	Periodontitis	Randomized; parallel assignment; double (participant investigator)	Dental pulp	Local injection at periodontal defect site	204	Single-dose group (DPSCs, 1.0 × 107); two-dose group (low-dose, DPSCs, 1.0 × 106); two-dose group (high-dose, DPSCs, 1.0 × 107)	Normal saline	90, 180, 360, 720 days	Phase 2
NCT05728346	Not yet recruiting	Pulp necroses	Nonrandomized; single group assignment; open label	Allogeneic deciduous pulp	Transplantation after the preparation and disinfection of the root canal of the affected teeth	30	SHED mixed with hyaluronic acid polymers	None	1, 3, 6, 12, 18, 24 months	Not applicable
NCT06043453	Recruiting	Apical periodontitis; trauma	Observational; multicenter blinded	Remaining dental pulp and apical papilla	Attraction or transplantation after root canal disinfection		With apical periodontitis	Without apical periodontitis	1, 2, 3 years	Not applicable
NCT04983225	Recruiting to active, not recruiting	Periodontitis	Randomized; parallel assignment; double-blind (participant, investigator)	Dental pulp	Injecting into the periodontal defect site	36	DPSCs (1 × 106)/site; DPSCs (5 × 106)/site; DPSCs [(3-4) × 107]/three or four sites; DPSCs (1 × 107)/site; DPSCs (2 × 107)/two sites	Saline solution	90, 180, 360, 720 days	Phase 1
NCT02523651	Unknown	Periodontitis	Randomized; parallel assignment; triple-blind (participant, investigator, outcomes assessor)	Allogeneic dental pulp	Injecting into the periodontal defect site	40	DPSCs (1 × 106)	Saline solution	1 year	Phase 1/2
NCT03386877	Completed	Periodontitis	Randomized; parallel assignment; triple-blind (participant, investigator, outcomes assessor)	Autologous dental pulp	Delivering into intrabony defect via minimally invasive surgical technique	29	Micrografts of DPSCs + collagen sponge	Collagen sponge	6, 12 months	Not applicable
NCT01082822	Unknown	Periodontitis	Nonrandomized; parallel assignment; open label	Periodontal ligament	Implanted into bone defect sites via surgical approach	80	PDLSCs sheet fragment + DBBM (Bio-oss); PDLSCs sheet pellets + DBBM (Bio-oss); DBBM (Bio-oss)	Sham comparator	4, 12, 24 weeks; 1 year	Phase 1/2
NCT03638154	Completed	Periodontitis	Randomized; parallel assignment; double-blind (care provider, outcomes assessor)	Gingival	Implanted into bone defect sites via surgical approach	20	GFs + GMSCs + β-TCP	β-TCP	1, 3, 7, 14 days; 6 months	Not applicable
NCT03137979	Unknown	Periodontitis	Randomized; parallel assignment	Gingival	Implanted into bone defect sites via surgical approach	30	GMSCs + collagen scaffolds; collagen scaffolds	Open flap debridement	1, 3, 6 months	Phase1/2
NCT01357785	Unknown	Periodontitis	Randomized; parallel assignment; open label	Autologous periodontal ligament		35		None	3-12 months	Phase1		Chen et al[174]
NCT04641533	Completed	Post-extraction sockets	Split-mouth; randomized; crossover assignment; double-blind (investigator, outcomes assessor)	Dental pulp	Placing into the extraction socket	13	DPSCs + L-PRF	L-PRF	7 days; 6 months	Not applicable		Cubuk et al[175]
NCT02731586	Unknown	Edentulous alveolar ridge	Single group assignment; open label	Allogeneic dental pulp	Introducing dental pulp-derived mesenchymal stem cells during placement of dental implants	10	Dental pulp-derived MSCs	None	3 months	Early phase 1
NCT03766217	Completed	Cleft lip and palate	Randomized; parallel assignment; single-blind (outcomes assessor)	Autologous deciduous pulp	Placed into the alveolar defect via surgical approach	62	SHED + hydroxyapatite-collagen sponge	Iliac crest autogenous bone graft	15 days; 3, 6, 12 months	Phase 3		Tanikawa et al[176], Pinheiro et al[177]
NCT01932164	Completed; has results	Cleft lip and palate	Single group assignment; open label	Autologous deciduous pulp	Maxillary alveolar graft by tissue engineering	5	SHED + hydroxyapatite-collagen sponge	None	3, 6 months	Not applicable	Percentage of bone filling at 6 months postoperatively: 89.5%	Tanikawa et al[176]
NCT04130100	Unknown	Knee osteoarthritis	Randomized; parallel assignment; open label	Dental pulp	Intraarticular injection	60	Low dose of DPSCs; high dose of DPSCs	Sodium hyaluronate	12 months	Early phase 1
NCT01814436	Unknown	Dental pulp necrosis	Single group assignment; open label	Autologous deciduous pulp		80	Scaffold-free SHED-derived pellet	None	3-12 months	Not applicable
NCT03957655	Unknown	Liver cirrhosis	Randomized; parallel assignment; single-blind (outcomes assessor)	Autologous deciduous pulp	Peripheral vein infusion	40	SHED (1 × 106 cells/kg body weight)	Standard medication for viral hepatitis and cirrhosis	4, 8, 12, 16, 24 weeks	Early phase 1
NCT03912480	Unknown	Type 1 diabetes	Single group assignment; open label	Deciduous pulp	Intravenous drip	24	SHED (0.11I U/kg body weight) + insulin + oral hypoglycemic drugs	None	1, 2, 6 weeks; 2, 3, 6, 9, 12 months	Early phase 1
NCT04608838	Completed	Acute ischemic stroke	Randomized; parallel assignment; quadruple-blind (participant, care provider, investigator, outcomes assessor)	Allogeneic dental pulp	Intravenously infusion	79	DPSCs (JTR-161, 1 × 108 cells); DPSCs (JTR-161, 3 × 108 cells)	Placebo	91, 366 days	Phase 1/2		Suda et al[178]
NCT02728115	Active, not recruiting to unknown		Nonrandomized; parallel assignment; open label	Allogeneic deciduous pulp	Intravenous administration	6	SHED (Cellavita HD, 1 × 106 cells); SHED (Cellavita HD, 2 × 106 cells)	None	1, 4 years	Phase 1
NCT04219241	Active, not recruiting to unknown	Huntington’s disease	Single group assignment; open label	Allogeneic deciduous pulp	Intravenous administration	35	SHED (Cellavita HD, 2 × 106 cells)	None	1, 2 years	Phase 2/3
NCT03252535	Completed	Huntington’s disease	Randomized; parallel assignment; triple-blind (participant, investigator, outcomes assessor)	Allogeneic deciduous pulp	Intravenous administration	35	SHED (Cellavita HD, 1 × 106 cells); SHED (Cellavita HD, 2 × 106 cells)	Physiological solution without cells	Monthly for 14 months	Phase 2		Wenceslau et al[179]
NCT04336254	Recruiting to unknown	COVID-19	Randomized; parallel assignment; triple-blind (participant, investigator, outcomes assessor)	Allogeneic dental pulp	Intravenous injection	20	DPSCs (3 × 107 cells)	Saline	28 days	Phase 1/2		Ye et al[180]
NCT04302519	Unknown	COVID-19	Single group assignment; open label	Dental pulp	Intravenous injection	24	DPSCs (1 × 107 cells/kg body weight)	None	3, 7, 14, 28, 360 days	Early phase 1

DPSCs: Dental pulp stem cells; SHED: Stem cells from human exfoliated deciduous teeth; PDLSCs: Periodontal ligament stem cells; DBBM: Deproteinized bovine bone mineral; GFs: Gingival fibroblast; GMSCs: Gingival mesenchymal stem cells; TCP: Tricalcium phosphate; PRF: Platelet-rich fibrin; MSCs: Mesenchymal stem cells; COVID-19: Coronavirus disease 2019.