Abstract
Dental stem cells are a minor population of mesenchymal stem cells existing in specialized dental tissues, such as dental pulp, periodontium, apical papilla, dental follicle and so forth. Standard methods have been established to isolate and identify these stem cells. Due to their differentiation potential, these mesenchymal stem cells are promising for tooth repair. Dental stem cells have been emerging to regenerated teeth and periodontal tissues, ascribe to their self-renewal, multipotency and tissue specific differentiation potential. Therefore, dental stem cells based regeneration medicine highlights a promising access to repair damaged dental tissues or generate new teeth. In this review, we provide an overview of human dental stem cells including isolation and identification, involved pathways and outcomes of regenerative researches. A number of basic researches, preclinical studies and clinical trials have investigated that dental stem cells efficiently improve formation of dental specialized structure and healing of periodontal diseases, suggesting a great feasibility and prospect of these approaches in translational medicine of dental regeneration.
Author contributed equally with all other contributors.Yi Shuai, Yang Ma and Tao Guo
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Abbreviations
- 3-D:
-
3-dimensional
- ALP:
-
alkaline phosphatase
- bFGF:
-
base fibroblast growth factor
- BMMSCs:
-
bone marrow mesenchymal stem cells
- BMP2:
-
bone morphogenetic protein 2
- BSP:
-
bone sialoprotein
- DFCs:
-
dental follicle cells
- DKK1:
-
Dickkopf 1
- DMP1:
-
dentin matrix protein1
- DNCPs:
-
dentin noncollagenous proteins
- DPSCs:
-
dental pulp stem cells
- ECM:
-
extracellular matrix
- EMD:
-
enamel matrix derivate
- GCN5:
-
general control nonrepressed protein 5
- G-CSF:
-
granulocyte colony-stimulating factor
- GTR:
-
guided tissue regeneration
- HA/TCP:
-
hydroxy apatite/tricalcium phosphate
- ICAM1:
-
intercellular adhesion molecule 1
- IGF-1:
-
insulin-like growth factor-1
- iPS:
-
induced pluripotent stem cells
- ITGB1:
-
integrin b1
- LPS:
-
lipopolysaccharide
- MAPK:
-
mitogen-activated protein kinase
- MEPE:
-
matrix extracellular phosphoglycoprotein
- OCN:
-
osteocalcin
- PDL:
-
periodontal ligament
- PDLSCs:
-
periodontal ligament stem cells
- PRP:
-
platelet rich plasma
- SCAPs:
-
stem cells from apical papilla
- SHEDs:
-
stem cells of human exfoliated deciduous teeth
- TDM:
-
treated dentin matrix; GMP: Good Manufacturing Practice.
- TERT:
-
telomerase reverse transcriptase
- TNF-α:
-
tumor necrosis factor-α
References
Ajay Sharma L, Sharma A, Dias GJ (2015) Advances in regeneration of dental pulp--a literature review. J Investig Clin Dent 6(2):85–98
An Y, Liu W, Xue P, Zhang Y, Wang Q, Jin Y (2016) Increased autophagy is required to protect periodontal ligament stem cells from apoptosis in inflammatory microenvironment. J Clin Periodontol 43(7):618–625
Andrei M, Dinischiotu A, Didilescu AC, Ionita D, Demetrescu I (2018) Periodontal materials and cell biology for guided tissue and bone regeneration. Ann Anat 216(164–169
Bakopoulou A, Leyhausen G, Volk J, Tsiftsoglou A, Garefis P, Koidis P et al (2011) Comparative analysis of in vitro osteo/odontogenic differentiation potential of human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAP). Arch Oral Biol 56(7):709–721
Chen FM, Gao LN, Tian BM, Zhang XY, Zhang YJ, Dong GY et al (2016) Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial. Stem Cell Res Ther 7:33
Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S et al (2008) Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod 34(8):962–969
Ding G, Liu Y, Wang W, Wei F, Liu D, Fan Z et al (2010) Allogeneic periodontal ligament stem cell therapy for periodontitis in swine. Stem Cells 28(10):1829–1838
Feng X, Feng G, Xing J, Shen B, Li L, Tan W et al (2013) TNF-alpha triggers osteogenic differentiation of human dental pulp stem cells via the NF-kappaB signalling pathway. Cell Biol Int 37(12):1267–1275
Feng X, Huang D, Lu X, Feng G, Xing J, Lu J et al (2014) Insulin-like growth factor 1 can promote proliferation and osteogenic differentiation of human dental pulp stem cells via mTOR pathway. Develop Growth Differ 56(9):615–624
Gronthos S, Mankani M, Brahim J, Robey PG, Shi S (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A 97(25):13625–13630
Guo W, Gong K, Shi H, Zhu G, He Y, Ding B et al (2012a) Dental follicle cells and treated dentin matrix scaffold for tissue engineering the tooth root. Biomaterials 33(5):1291–1302
Guo W, Chen L, Gong K, Ding B, Duan Y, Jin Y (2012b) Heterogeneous dental follicle cells and the regeneration of complex periodontal tissues. Tissue Eng Part A 18(5–6):459–470
Hamano S, Tomokiyo A, Hasegawa D, Yoshida S, Sugii H, Mitarai H et al (2018) Extracellular matrix from periodontal ligament cells could induce the differentiation of induced pluripotent stem cells to periodontal ligament stem cell-like cells. Stem Cells Dev 27(2):100–111
Han C, Yang Z, Zhou W, Jin F, Song Y, Wang Y et al (2010) Periapical follicle stem cell: a promising candidate for cementum/periodontal ligament regeneration and bio-root engineering. Stem Cells Dev 19(9):1405–1415
Han J, Menicanin D, Marino V, Ge S, Mrozik K, Gronthos S et al (2014) Assessment of the regenerative potential of allogeneic periodontal ligament stem cells in a rodent periodontal defect model. J Periodontal Res 49(3):333–345
He W, Wang Z, Luo Z, Yu Q, Jiang Y, Zhang Y et al (2015) LPS promote the odontoblastic differentiation of human dental pulp stem cells via MAPK signaling pathway. J Cell Physiol 230(3):554–561
Hilkens P, Gervois P, Fanton Y, Vanormelingen J, Martens W, Struys T et al (2013) Effect of isolation methodology on stem cell properties and multilineage differentiation potential of human dental pulp stem cells. Cell Tissue Res 353(1):65–78
Hjorting-Hansen E (2002) Bone grafting to the jaws with special reference to reconstructive preprosthetic surgery. A historical review. Mund Kiefer Gesichtschir 6(1):6–14
Huang AH, Chen YK, Lin LM, Shieh TY, Chan AW (2008) Isolation and characterization of dental pulp stem cells from a supernumerary tooth. J Oral Pathol Med 37(9):571–574
Huang GT, Yamaza T, Shea LD, Djouad F, Kuhn NZ, Tuan RS et al (2010) Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Eng Part A 16(2):605–615
Iohara K, Nakashima M, Ito M, Ishikawa M, Nakasima A, Akamine A (2004) Dentin regeneration by dental pulp stem cell therapy with recombinant human bone morphogenetic protein 2. J Dent Res 83(8):590–595
Iohara K, Murakami M, Takeuchi N, Osako Y, Ito M, Ishizaka R et al (2013) A novel combinatorial therapy with pulp stem cells and granulocyte colony-stimulating factor for Total pulp regeneration. Stem Cells Transl Med 2(10):818
Ji K, Liu Y, Lu W, Yang F, Yu J, Wang X et al (2013) Periodontal tissue engineering with stem cells from the periodontal ligament of human retained deciduous teeth. J Periodontal Res 48(1):105–116
Kawashima N (2012) Characterisation of dental pulp stem cells: a new horizon for tissue regeneration? Arch Oral Biol 57(11):1439–1458
Kim SH, Kim KH, Seo BM, Koo KT, Kim TI, Seol YJ et al (2009) Alveolar bone regeneration by transplantation of periodontal ligament stem cells and bone marrow stem cells in a canine peri-implant defect model: a pilot study. J Periodontol 80(11):1815–1823
Kunimatsu R, Nakajima K, Tetsuya A, Tsuka Y, Abe T, Ando K et al (2018) Comparative characterization of stem cells from human exfoliated deciduous teeth, dental pulp, and bone marrow-derived mesenchymal stem cells. Biochem Biophys Res Commun 501:193–198
Li J, Yan M, Wang Z, Jing S, Li Y, Liu G et al (2014a) Effects of canonical NF-kappaB signaling pathway on the proliferation and odonto/osteogenic differentiation of human stem cells from apical papilla. Biomed Res Int 2014:319651
Li Y, Yan M, Wang Z, Zheng Y, Li J, Ma S et al (2014b) 17beta-estradiol promotes the odonto/osteogenic differentiation of stem cells from apical papilla via mitogen-activated protein kinase pathway. Stem Cell Res Ther 5(6):125
Li B, Sun J, Dong Z, Xue P, He X, Liao L et al (2016) GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment. Sci Rep 6:26542
Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM et al (2008) Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem Cells 26(4):1065–1073
Liu Y, Liu W, Hu C, Xue Z, Wang G, Ding B et al (2011) MiR-17 modulates osteogenic differentiation through a coherent feed-forward loop in mesenchymal stem cells isolated from periodontal ligaments of patients with periodontitis. Stem Cells 29(11):1804–1816
Liu J, Wang L, Liu W, Li Q, Jin Z, Jin Y (2014) Dental follicle cells rescue the regenerative capacity of periodontal ligament stem cells in an inflammatory microenvironment. PLoS One 9(9):e108752
Liu Q, Hu CH, Zhou CH, Cui XX, Yang K, Deng C et al (2015) DKK1 rescues osteogenic differentiation of mesenchymal stem cells isolated from periodontal ligaments of patients with diabetes mellitus induced periodontitis. Sci Rep 5:13142
Ma Z, Li S, Song Y, Tang L, Ma D, Liu B et al (2008) The biological effect of dentin noncollagenous proteins (DNCPs) on the human periodontal ligament stem cells (HPDLSCs) in vitro and in vivo. Tissue Eng Part A 14(12):2059–2068
Ma L, Makino Y, Yamaza H, Akiyama K, Hoshino Y, Song G et al (2012) Cryopreserved dental pulp tissues of exfoliated deciduous teeth is a feasible stem cell resource for regenerative medicine. PLoS One 7(12):e51777
Mao CY, Wang YG, Zhang X, Zheng XY, Tang TT, Lu EY (2016) Double-edged-sword effect of IL-1beta on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF-kappaB, MAPK and BMP/Smad signaling pathways. Cell Death Dis 7:e2296
Miron RJ, Sculean A, Cochran DL, Froum S, Zucchelli G, Nemcovsky C et al (2016) Twenty years of enamel matrix derivative: the past, the present and the future. J Clin Periodontol 43(8):668–683
Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG et al (2003) SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 100(10):5807–5812
Morsczeck C, Gotz W, Schierholz J, Zeilhofer F, Kuhn U, Mohl C et al (2005) Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol 24(2):155–165
Nakamura S, Yamada Y, Katagiri W, Sugito T, Ito K, Ueda M (2009) Stem cell proliferation pathways comparison between human exfoliated deciduous teeth and dental pulp stem cells by gene expression profile from promising dental pulp. J Endod 35(11):1536–1542
Nakashima M, Iohara K, Murakami M, Nakamura H, Sato Y, Ariji Y et al (2017) Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: a pilot clinical study. Stem Cell Res Ther 8(1):61
Napimoga MH, Nametala C, da Silva FL, Miranda TS, Bossonaro JP, Demasi AP et al (2014) Involvement of the Wnt-beta-catenin signalling antagonists, sclerostin and dickkopf-related protein 1, in chronic periodontitis. J Clin Periodontol 41(6):550–557
Needleman IG, Worthington HV, Giedrys-Leeper E, Tucker RJ (2006) Guided tissue regeneration for periodontal infra-bony defects. Cochrane Database Syst Rev 2:CD001724
Ostby BN (1961) The role of the blood clot in endodontic therapy. An experimental histologic study. Acta Odontol Scand 19:324–353
Papaccio G, Graziano A, D'Aquino R, Graziano MF, Pirozzi G, Menditti D et al (2006) Long-term cryopreservation of dental pulp stem cells (SBP-DPSCs) and their differentiated osteoblasts: a cell source for tissue repair. J Cell Physiol 208(2):319–325
Park BW, Jang SJ, Byun JH, Kang YH, Choi MJ, Park WU et al (2017) Cryopreservation of human dental follicle tissue for use as a resource of autologous mesenchymal stem cells. J Tissue Eng Regen Med 11(2):489–500
Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366(9499):1809–1820
Prescott RS, Alsanea R, Fayad MI, Johnson BR, Wenckus CS, Hao J et al (2008) In vivo generation of dental pulp-like tissue by using dental pulp stem cells, a collagen scaffold, and dentin matrix protein 1 after subcutaneous transplantation in mice. J Endod 34(4):421–426
Rosa V, Zhang Z, Grande RH, Nor JE (2013) Dental pulp tissue engineering in full-length human root canals. J Dent Res 92(11):970–975
Scheller EL, Chang J, Wang CY (2008) Wnt/beta-catenin inhibits dental pulp stem cell differentiation. J Dent Res 87(2):126–130
Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J et al (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364(9429):149–155
Seo BM, Miura M, Sonoyama W, Coppe C, Stanyon R, Shi S (2005) Recovery of stem cells from cryopreserved periodontal ligament. J Dent Res 84(10):907–912
Sharpe PT (2016) Dental mesenchymal stem cells. Development 143(13):2273–2280
Silverio KG, Rodrigues TL, Coletta RD, Benevides L, Da Silva JS, Casati MZ et al (2010) Mesenchymal stem cell properties of periodontal ligament cells from deciduous and permanent teeth. J Periodontol 81(8):1207–1215
Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C et al (2006) Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One 1:e79
Sonoyama W, Liu Y, Yamaza T, Tuan RS, Wang S, Shi S et al (2008) Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod 34(2):166–171
Sowmya S, Chennazhi KP, Arzate H, Jayachandran P, Nair SV, Jayakumar R (2015) Periodontal specific differentiation of dental follicle stem cells into osteoblast, fibroblast, and cementoblast. Tissue Eng Part C Methods 21(10):1044–1058
Suchanek J, Soukup T, Visek B, Ivancakova R, Kucerova L, Mokry J (2009) Dental pulp stem cells and their characterization. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 153(1):31–35
Sun F, Wan M, Xu X, Gao B, Zhou Y, Sun J et al (2014) Crosstalk between miR-34a and notch signaling promotes differentiation in apical papilla stem cells (SCAPs). J Dent Res 93(6):589–595
Sun J, Dong Z, Zhang Y, He X, Fei D, Jin F et al (2017a) Osthole improves function of periodontitis periodontal ligament stem cells via epigenetic modification in cell sheets engineering. Sci Rep 7(1):5254
Sun J, Li J, Li H, Yang H, Chen J, Yang B et al (2017b) tBHQ suppresses osteoclastic resorption in xenogeneic-treated dentin matrix-based scaffolds. Adv Healthc Mater 6(18)
Sununliganon L, Singhatanadgit W (2012) Highly osteogenic PDL stem cell clones specifically express elevated levels of ICAM1, ITGB1 and TERT. Cytotechnology 64(1):53–63
Trubiani O, Di Primio R, Traini T, Pizzicannella J, Scarano A, Piattelli A et al (2005) Morphological and cytofluorimetric analysis of adult mesenchymal stem cells expanded ex vivo from periodontal ligament. Int J Immunopathol Pharmacol 18(2):213–221
Wada N, Menicanin D, Shi S, Bartold PM, Gronthos S (2009) Immunomodulatory properties of human periodontal ligament stem cells. J Cell Physiol 219(3):667–676
Wang Y, Yan M, Yu Y, Wu J, Yu J, Fan Z (2013) Estrogen deficiency inhibits the odonto/osteogenic differentiation of dental pulp stem cells via activation of the NF-kappaB pathway. Cell Tissue Res 352(3):551–559
Wang P, Wang Y, Tang W, Wang X, Pang Y, Yang S et al (2017) Bone morphogenetic Protein-9 enhances osteogenic differentiation of human periodontal ligament stem cells via the JNK pathway. PLoS One 12(1):e0169123
Wang H, Zhong Q, Yang T, Qi Y, Fu M, Yang X et al (2018a) Comparative characterization of SHED and DPSCs during extended cultivation in vitro. Mol Med Rep 17(5):6551–6559
Wang Y, Pang X, Wu J, Jin L, Yu Y, Gobin R et al (2018b) MicroRNA hsa-let-7b suppresses the odonto/osteogenic differentiation capacity of stem cells from apical papilla by targeting MMP1. J Cell Biochem 119:6545–6554
Winning L, Linden GJ (2017) Periodontitis and systemic disease: association or causality? Curr Oral Health Rep 4(1):1–7
Wu J, Huang GT, He W, Wang P, Tong Z, Jia Q et al (2012) Basic fibroblast growth factor enhances stemness of human stem cells from the apical papilla. J Endod 38(5):614–622
Xue P, Li B, An Y, Sun J, He X, Hou R et al (2016) Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation. Cell Death Differ 23(11):1862–1872
Yang N, Li Y, Wang G, Ding Y, Jin Y, Xu Y (2017) Tumor necrosis factor-alpha suppresses adipogenic and osteogenic differentiation of human periodontal ligament stem cell by inhibiting miR-21/Spry1 functional axis. Differentiation 97(33–43
Yao S, Pan F, Prpic V, Wise GE (2008) Differentiation of stem cells in the dental follicle. J Dent Res 87(8):767–771
Zhang W, Yelick PC (2010) Vital pulp therapy-current progress of dental pulp regeneration and revascularization. Int J Dent 2010(856087):1–9
Zhang W, Walboomers XF, van Kuppevelt TH, Daamen WF, Bian Z, Jansen JA (2006) The performance of human dental pulp stem cells on different three-dimensional scaffold materials. Biomaterials 27(33):5658–5668
Zhang H, Liu S, Zhou Y, Tan J, Che H, Ning F et al (2012) Natural mineralized scaffolds promote the dentinogenic potential of dental pulp stem cells via the mitogen-activated protein kinase signaling pathway. Tissue Eng Part A 18(7–8):677–691
Zhang H, Wang J, Deng F, Huang E, Yan Z, Wang Z et al (2015) Canonical Wnt signaling acts synergistically on BMP9-induced osteo/odontoblastic differentiation of stem cells of dental apical papilla (SCAPs). Biomaterials 39(145–154
Acknowledgements
This work was financially supported by grants from the Nature Science Foundation of China (81620108007) and the National Natural Science Foundation of China (31571532).
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All the authors declare that they have no competing interests.
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Shuai, Y. et al. (2018). Dental Stem Cells and Tooth Regeneration. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 3. Advances in Experimental Medicine and Biology(), vol 1107. Springer, Cham. https://doi.org/10.1007/5584_2018_252
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DOI: https://doi.org/10.1007/5584_2018_252
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