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©The Author(s) 2023.
World J Stem Cells. Mar 26, 2023; 15(3): 31-51
Published online Mar 26, 2023. doi: 10.4252/wjsc.v15.i3.31
Published online Mar 26, 2023. doi: 10.4252/wjsc.v15.i3.31
Cell types | Markers | Multidirectional differentiations | ||
Cell surface markers | Embryonic stem cell markers | Nerual markers | ||
DPSCs | CD13, CD29, CD44, CD59, CD73, CD90, CD105, CD146, STRO-1[7], CD81, CD49f[140], CD40, CD120a, CD261, CD262, CD264, CD266, CD121a, CD130, CD213a1, CD217, CDw210b[141] | OCT-4, Nanog[142], SSEA-1, SEEA-4[140], SOX-2[143] | βIII-tubulin, NFM, Nestin, CNPase[144], S100, CD271[17] | Osteogenic, Odontogenic[145], Dentinogeni, Chondrogenic, Neurogenic, Myogenic, Adipogenic[13], Hepatogenic[146] |
PDLSCs | CD13, CD29, CD44, CD49, CD73, CD90, CD105, CD146, CD166, CD271[147], CD10[7], STRO-1[148] | SSEA-1, SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, OCT-4, Nanog, SOX-2, REX1, and ALP[149] | Nestin, OCT-4, SSEA-4[9] CD271, SOX-10[147], SOX-2[149] | Osteogenic, Cementogenic, Adipogenic, Chondrogenic, Neurogenic[13], Hepatogenic[149], Cardiac myogenic, Endothelial-like, Islet-like, Retinal ganglion-like[147] |
SCAP | CD13, CD24, CD29, CD44, CD49, CD51, CD56, CD61, CD73, CD90, CD105, CD106, CD146, CD166, STRO-1, NOTCH-3[150], CD81, CD49f[151] | OCT-4, Nanog, SOX2[143], CD49f[151] | βIII-tubulin, NFM, Nestin, CNPase[144], SOX-2[143], Vimentin, Survivin[150] | Osteogenic, Dentinogenic, Adipogenic[15], Neurogenic[13], Chondrogenic, Hepatogenic[150] |
SHED | CD29, CD73, CD90, CD166[13], STRO-1, CD44[145], CD105[152], NOTCH-1, CD10, CD13, CD34, CD106, CD146, CD166, CD271[102] | OCT-4, Nanog, SSEA-3[153], SSEA-4[152], NOTCH-1, OCT-4, SOX-2[102] | βIII-tubulin, NFM, Nestin, CNPase, GAD, NeuN, GFAP[154], CD271, Vimentin, OCT-4, PAX-6, NSE, MAP-2, PSA-NCAM, TH[102] | Osteogenic, Odontogenic[145], Dentinogenic, Chondrogenic, Neurogenic, Myogenic, Adipogenic[13], Hepatogenic[155] |
DFPCs | CD13, CD29, CD59, CD90[7], CD105, CD146[142], CD44, CD73, NOTCH-1, STRO-1[156] | OCT-4, Nanog[142], NOTCH-1, SOX-2[156] | OCT-4, SOX2[9], Nestin, SOX-2[156] | Osteogenic, Cementogenic, Odontogenic, Adipogenic, Chondrogenic[13], Hepatogenic[146] |
GMSCs | CD13, CD29, CD44, CD73, CD90, CD105, CD146, STRO-1[16] | SSEA-4[16], OCT-4, Nanog[157] | Nestin, SOX10[16], βIII-tubulin, NFM, CNPase[144] | Osteogenic, Adipogenic, Chondrogenic, Neurogenic, Endothelial-like, Odontogenic[16], Myogenic[158] |
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 |
Ref. | Registration ID | Status | Diseases | Study design | Cell source | Administration route | Number of patients | Interventions | Follow-upperiod | Phase | Outcomes | |
Test group | Control group | |||||||||||
- | NCT04983225 | 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 d | 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 mo | 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 wk; 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 d; 6 mo | 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 mo | Phase1/2 | |
Chen et al[29], 2016 | NCT01357785 | Unknown | Periodontitis | Randomized; parallel assignment; open label | Autologous periodontal ligament | 35 | None | 3-12 mo | Phase1 | |||
Cubuk et al[62], 2023 | 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 d; 6 mo | Not applicable | |
- | 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 mo | Early Phase 1 | |
Tanikawa et al[63], 2020; Pinheiro et al[70], 2019 | 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 d; 3, 6, 12 mo | Phase3 | |
Tanikawa et al[63], 2020 | 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 mo | Not applicable | Percentage of bone filling at 6 mo postoperatively: 89.5% |
- | 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 mo | 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 mo | 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 wk | Early phase 1 | |
- | NCT03912480 | Unknown | Type 1 diabetes | Single group assignment; open label | Deciduous pulp | Intravenous drip | 24 | SHED (0.11 IU/kg body weight) + Insulin + oral hypoglycemic drugs | None | 1, 2, 6 wk; 2, 3, 6, 9, 12 mo | Early phase 1 | |
Suda et al[67], 2022 | 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 d | Phase 1/2 | |
- | NCT02728115 | Active, not recruiting | 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 | 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 | |
Wenceslau et al[71], 2022 | 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 mo | Phase 2 | |
Ye et al[69], 2020 | NCT04336254 | Recruiting | COVID-19 | Randomized; parallel assignment; triple-blind (participant, investigator, outcomes assessor) | Allogeneic dental pulp | Intravenous injection | 20 | DPSCs (3 × 107 cells) | Saline | 28 d | Phase 1/2 | |
- | 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 d | Early phase 1 |
Ref. | Registration ID | Status | Diseases | Study design | Cell source | Administration route | Number of patients | Interventions | Follow-up period | Phase | Outcomes | |
Test group | Control group | |||||||||||
- | JPRN-UMIN000042791 | Complete: Follow-up complete | Periodontitis | Randomized; parallel assignment; single-blind (participants) | Deciduous pulp | Gargle | 30 | Mouthwash containing SHED culture supernatant | Mouthwash without SHED culture supernatant | 1 mo | Not applicable | |
- | ChiCTR2100051466 | Recruiting | Periodontitis | Randomized; parallel assignment; open label | Dental pulp | Bilateral multipoint injection on a single tooth | 96 | DPSCs (1 × 107 cells) for once; DPSCs (1 × 107 cells) for twice | Saline | 90, 180, 360 d | Phage 0 | |
- | ChiCTR2100049178 | Pending | Periodontitis | Randomized; parallel assignment; double-blind | Dental pulp | Local injection | 36 | DPSCs (1 × 106 cells) for single injection; DPSCs (5 × 106 cells) for single injection; DPSCs (1 × 107 cells) for single injection; DPSCs (1 × 107 cells) for single injection in 2 locations; DPSCs (1 × 107 cells) for single injection in 3-4 locations | None | Phage 1 | ||
Sánchez et al[42], 2020 | ISRCTN13093912 | Completed | Periodontitis | Randomized; parallel assignment; single-blind (patients and examiners) | Dental pulp | Implanted into bone defect sites via surgical approach | 20 | DPSCs (1 × 107 cells) + hydroxyapatite-collagen scaffold | Hydroxyapatite-collagen scaffold | 1, 2, 4, 12, 24, 36 wk; 12, 24, 36, 48, 60 mo | Not applicable | |
- | JPRN-UMIN000045926 | Complete: Follow-up complete | Wrinkles | Randomized; parallel assignment; single-blind (outcomes assessor) | Dental pulp | 12 | All-in-one gel containing immortalized DPSCs-CM solution and various beauty ingredients | No treatment | 4 wk | Not applicable | ||
- | JPRN-UMIN000043528 | Complete: Follow-up complete | Wrinkles | Randomized; parallel assignment; single-blind (outcomes assessor) | Dental pulp | 12 | All-in-one gel containing immortalized DPSC-CM solution and the latest peptide raw materials | No treatment | 4 wk | Not applicable | ||
- | JPRN-UMIN000045897 | Complete: Follow-up continuing | Hair loss | Nonrandomized; parallel assignment; open label | Deciduous pulp | Injection | 22 | SHED-CM; after SHED-CM injection, one dose of micrografts (Rigenera) followed by another SHED-CM injection; SHED-CM injection after one dose of micrografts (Rigenera) | None | 6 mo | Not applicable |
- Citation: Song WP, Jin LY, Zhu MD, Wang H, Xia DS. Clinical trials using dental stem cells: 2022 update. World J Stem Cells 2023; 15(3): 31-51
- URL: https://www.wjgnet.com/1948-0210/full/v15/i3/31.htm
- DOI: https://dx.doi.org/10.4252/wjsc.v15.i3.31