Clinical trials using dental stem cells: 2022 update

Table 2 Dental stem cell-based clinical trials from published articles

Ref.	Registration ID	Conditions/diseases	Study design	Cell source	Administration route	Interventions		Follow-up period	Outcomes
						Test group	Control group
Xuan et al[28], 2018	NCT01814436	Pulp necrosis	RCT	Autologous deciduous pulp	Implanted into injured teeth	SHED (n = 26)	Traditional apexification treatment (n = 10)	12 mo; 24 mo	Dental pulp tissue regeneration; no adverse events observed; the length of the root (↑); the width of the apical foramen (↓)
Nakashima et al[35], 2022	None	Irreversible pulpitis	Case series	Autologous dental pulp	Transplanted into the root canal	DPSCs + Gelatin sponge + G-CSF (n = 5)	None	1, 2, 4, 12, 24, 28, 32 wk	Pulp sensibility (↑); MRI examination showed similar SI between test teeth and untreated controls
Nakashima et al[37], 2017	None	Irreversible pulpitis	Case series	Autologous dental pulp	Transplanted into the root canal	DPSCs + Gelatin sponge + G-CSF (n = 2)	None	1, 4, 12, 24, and 48 wk	MRI examination showed similar SI between test teeth and untreated controls; mineralized tissue deposition (↑)
Meza et al[36], 2019	None	Irreversible pulpitis	A case report	Autologous inflamed dental pulp	Transplanted into the root canal	DPSCs + L-PRF (n = 1)	None	6 mo; 3 year	Delayed response to the cold test; positive response to electric pulp testing; dentin bridge formation
Shiehzadeh et al[38], 2014	None	Periapical lesions	Case series	Case 1 and case 3: Autologous apical papilla; case 2: Deciduous pulp	Case 1 and Case 3: Injected from root apex to cavity; case 2: Injected into the defect via a surgical approach	Case 1 and Case 3: SCAP + PEG-PLGA scaffold (n = 2); case 2: SHED + PEG-PLGA scaffold (n = 1)	None	Case 1: 30 d, 3 mo, 1 year; 2 year; case 2: 3, 6, 18 mo; case 3: 3, 6, 12, 24 mo	Developed mature apices; periapical tissue healing (↑)
Prasad et al[39], 2017	None	Periapical lesions	Case series	Allogeneic deciduous pulp	Transplanted into the root canal	SHED + Bioglass (n = 2)	None	7, 30, 90, 180, 365 d	Closure of open apex; periapical tissue healing; positive response to electric pulp testing and cold testing
Prasad et al[40], 2019	None	Periapical lesions	A case report	Allogeneic deciduous pulp	Transplanted into the root canal and periapical area	SHED + Bioglass (n = 1)	None	2 wk; 4, 12, 24 mo	Periapical tissue healing; positive response to electric pulp testing
Ferrarotti et al[41], 2018	NCT03386877	Periodontal intrabony defects	RCT	Autologous dental pulp	Implanted into bone defect sites consisted of MIST	Pulp micrografts + Collagen sponge (n = 15)	Collagen sponge (n = 14)	6 and 12 mo	PD (↓); CAL (↓); bone defect fill (↑); residual PD < 5 mm and CAL gain ≥ 4 mm (↑)
Sánchez et al[42], 2020	ISRCTN13093912	Periodontal intrabony defects	CCT	Autologous periodontal ligament	Implanted into bone defect sites via surgical approach	PDLSCs + β-TCP (n = 9)	β-TCP (n = 10)	1, 3, 6, 9, 12 mo	CAL (-); PPD (-)
Feng et al[43], 2010	None	Periodontal intrabony defects	Case series	Autologous periodontal ligament	Implanted into bone defect sites via surgical approach	PDLPs + HA/TCP (n = 3)	None	3, 6, 12, 32, 42, and 72 mo	CAL (↓); PD (↓); GR (↑)
Chen et al[29], 2016	NCT01357785	Periodontal intrabony defects	RCT	Autologous periodontal ligament	Implanted into bone defect sites via surgical approach	PDLSCs sheets + DBBM (n = 20)	DBBM (n = 21)	2 wk; 3, 6, 12 mo	CAL (-); PD (-); GR (-)
Iwata et al[44], 2018	UMIN000005027	Periodontal intrabony defects	Case series	Autologous periodontal ligament	Implanted into bone defect sites via surgical approach	PDL-derived cell sheets + β-TCP (n = 10)	None	3, 6, 55 ± 19 mo	CAL (↓); PD (↓); bone height (↑)
Vandana et al[125], 2015	None	Periodontal intrabony defects	A case report	Autologous periodontal ligament	Implanted into bone defect sites via surgical approach	Periodontal ligament soft tissue + Gelatin sponge + Cementum scrapings (n = 1)	None	1 wk; 3, 6, 12 mo	CAL (↓); PD (↓); BMD (↑)
Aimetti et al[47], 2014	None	Periodontal intrabony defects	A case report	Autologous dental pulp	Implanted into bone defect sites via surgical approach	Pulp micrografts + Collagen sponge (n = 1)	None	6 mo; 1 year	PPD (↓); bone fill (↑)
Aimetti et al[46], 2018	None	Periodontal intrabony defects	Case series	Autologous dental pulp	Implanted into bone defect sites via surgical approach	Pulp micrografts + Collagen sponge (n = 11)	None	1 year	CAL (↓); PD (↓); bone fill (↑)
Aimetti et al[49], 2015	None	Periodontal intrabony defects	Case series	Autologous dental pulp	Implanted into bone defect sites via surgical approach	Pulp micrografts + Collagen sponge (n = 4)	None	6, 12 mo	PD (↓); CAL (↓); bone fill (↑)
Hernández-Monjaraz et al[48], 2018	ISRCTN12831118	Periodontal intrabony defects	A case report	Allogeneic dental pulp	Implanted into bone defect sites via surgical approach	DPSCs + Lyophilized collagen-polyvinylpyrrolidone sponge scaffold (n = 1)	None	3, 6 mo	PD (↓); TM (↓); bone fill (↑)
Barbier et al[57], 2018	EudraCT database 2014-001913-18	Post-extraction sockets	Split-mouth RCT	Autologous dental pulp	Implanted into postextraction sockets	Pulp micrografts + collagen matrix (n = 30)	Collagen matrix (n = 30)	6 mo	BMD (-); interdental septum height (-)
Cubuk et al[62], 2023	NCT04641533	Post-extraction sockets	Split-mouth RCT	Autologous dental pulp	Implanted into postextraction sockets	Pulp micrografts + L-PRF (n = 13)	L-PRF (n = 13)	7 d; 6 mo	PPD (-); CAL (-); vertical bone loss (-); relative bone density (-)
d’Aquino et al[58], 2009	None	Post-extraction sockets	Split-mouth CCT	Autologous dental pulp	Implanted into postextraction sockets	Dental pulp stem/progenitor cells + collagen sponge (n = 7)	Collagen sponge (n = 7)	7 d; 1, 2, 3, 12 mo	Rate of mineralization (↑); levels of cortical bone (↑); CAL (↓); BMP-2, VEGF (↑)
Tanikawa et al[63], 2020	NCT03766217	Cleft lip and palate	Historical control study	Autologous deciduous pulp	Placed into the alveolar defect via surgical approach	SHED + Hydroxyapatite-collagen sponge (n = 6)	rhBMP-2 + Hydroxyapatite-collagen sponge (Group I n = 8); Iliac crest bone graft (Group II n = 8)	6, 12 mo	Bone filling percentage (↑, compared with Group I at the 6-mo follow-up)
Manimaran et al[59], 2014	None	Mandibular osteoradionecrosis	A case report	Allogeneic dental pulp	Inserted into the defect after surgical curettage	DPSCs + PRP + TCP (n = 1)	None	2, 6 mo	Bone formation (↑)
Manimaran et al[60], 2016	None	Bone defect left by the resection of mandibular ameloblastoma	A case report	Autologous dental pulp	Packed inside the mesh and placed over the mandible after tumor resection	DPSCs + β-TCP + PRF + SVF (n = 1)	None	1, 10 mo; 1.5 years	Bone regeneration (↑); no recurrence of tumor
Brunelli et al[61], 2013	None	Sinus lifting	A case report	Autologous dental pulp	Implanted into sinus cavity	Pulp micrografts + Collagen sponge (n = 1)	None	4 mo	BMD (↑)
Koga et al[64], 2022	None	Erectile dysfunction	Case series	Allogeneic deciduous pulp	Injected into the penis	SHED-CM (n = 38)	None	After every injection	IIEF-5 score (↑)
Silva et al[65], 2022	NCT02728115	Huntington’s disease with preexisting pulmonary nodule	A case report	Allogeneic deciduous pulp	Intravenous administrations	SHED (n = 1)	None	15, 30 d; 7, 24, 32 mo	Unified Huntington’s disease rating scale (↓); not show long-term tropism or homing for the lung adenocarcinoma
Wang et al[93], 2010	None	Plaque psoriasis	A case report	Allogeneic gingival	Bolus injection	GMSCs (n = 1)	None	3 years	Psoriatic lesions fully cleared; no recurrence
Suda et al[67], 2022	NCT04608838; JapicCTI194570	Acute ischemic stroke	Study protocol	Allogeneic dental pulp	Intravenous administration	DPSCs	Placebo	Per 15 min (1-4 h); per 30 min (4-6 h); 12, 24 h; 2, 3, 8, 31, 91, 181, 366 d	No results
Nagpal et al[68], 2016	None	Chronic disability after stroke	Study protocol	Autologous dental pulp	Implanted into peri-infarct region via neurosurgical procedure	DPSCs	None	1, 6, 9, 12 mo	No results
Ye et al[69], 2020	ChiCTR2000031319: NCT04336254	COVID-19	Study protocol	Allogeneic dental pulp	Intravenous administration	DPSCs	Saline	2 h ± 30 min; 24 h ± 30 min; 90 d ± 3 d	No results

BMD: Bone mineral density; CAL: Clinical attachment level; CCT: Controlled clinical trials; COVID-19: Coronavirus disease 2019; DBBM: Deproteinized bovine bone mineral; GR: Gingival recession; G-CSF: Granulocyte colony stimulating factor; HA/TCP: Hydroxyapatite/tricalcium phosphate; IIEF: International index of erectile function; L-PRF: Leukocyte-platelet rich fibrin; MIST: Minimally invasive surgical technique; MRI: Magnetic resonance imaging; PD: Probing depth; PDL: Periodontal ligament; PDLPs: Periodontal ligament progenitor cells; PPD: Periodontal probing depth; PRF: Platelet rich fibrin; PRP: Platelet-rich plasma; PEG-PLGA: Poly (lactide-co glycolide)-polyethylene glycol; RCT: Random clinical trial; rh-BMP: Recombinant human bone morphogenetic protein; SI: Signal intensity; SVF: Stromal vascular fraction: TCP: Tricalcium phosphate; TM: Tooth mobility; VEGF: Vascular endothelial growth factor; SHED-CM: Stem cells from exfoliated deciduous teeth conditioned medium.