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Dental stem cell and dental tissue regeneration

  • Qiming Zhai 1 ,
  • Zhiwei Dong 3 ,
  • Wei Wang 4 ,
  • Bei Li , 1,2 ,
  • Yan Jin , 1,2
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  • 1. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Center for Tissue Engineering, Fourth Military Medical University, Xi’an 710032, China
  • 2. Xi’an Institute of Tissue Engineering and Regenerative Medicine, Xi’an 710032, China
  • 3. Department of Oral and Maxillofacial Surgery, General Hospital of Shenyang Military Area Command, Shenyang 110840, China
  • 4. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Xi’an 710032, China

Received date: 28 Aug 2017

Accepted date: 14 Dec 2017

Published date: 28 Mar 2019

Copyright

2018 Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature

Abstract

The teeth are highly differentiated chewing organs formed by the development of tooth germ tissue located in the jaw and consist of the enamel, dentin, cementum, pulp, and periodontal tissue. Moreover, the teeth have a complicated regulatory mechanism, special histologic origin, diverse structure, and important function in mastication,, articulation,, and aesthetics. These characteristics, to a certain extent, greatly complicate the research in tooth regeneration. Recently, new ideas for tooth and tissue regeneration have begun to appear with rapid developments in the theories and technologies in tissue engineering. Numerous types of stem cells have been isolated from dental tissue, such as dental pulp stem cells (DPSCs), stem cells isolated from human pulp of exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAPs), and dental follicle cells (DFCs). All these cells can regenerate the tissue of tooth. This review outlines the cell types and strategies of stem cell therapy applied in tooth regeneration, in order to provide theoretical basis for clinical treatments.

Cite this article

Qiming Zhai, Zhiwei Dong, Wei Wang, Bei Li, Yan Jin. Dental stem cell and dental tissue regeneration[J]. Frontiers of Medicine, 2019, 13(2): 152-159. DOI: 10.1007/s11684-018-0628-x

Acknowledgements

This work was supported by the grants from the National Natural Science Foundation of China (Nos. 31501121, 31401255, 81570976, and 31500786) and Natural Science Foundation research project of Shaanxi Province (Nos. 2016JQ8019 and 016KW-005).

Compliance with ethics guidelines

Qiming Zhai, Zhiwei Dong, Wei Wang, Bei Li, and Yan Jin declare that they have no conflict of interest or financial conflicts to disclose. This manuscript is a review article and did not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.
1
Catón J, Bostanci N, Remboutsika E, De Bari C, Mitsiadis TA. Future dentistry: cell therapy meets tooth and periodontal repair and regeneration. J Cell Mol Med 2011; 15(5): 1054–1065

DOI PMID

2
Yoshida T, Washio K, Iwata T, Okano T, Ishikawa I. Current status and future development of cell transplantation therapy for periodontal tissue regeneration. Int J Dent 2012;2012:307024

DOI

3
Liu N, Shi S, Deng M, Tang L, Zhang G, Liu N, Ding B, Liu W, Liu Y, Shi H, Liu L, Jin Y. High levels of b-catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway. J Bone Miner Res 2011; 26(9): 2082–2095

DOI PMID

4
Liu Y, Liu W, Hu C, Xue Z, Wang G, Ding B, Luo H, Tang L, Kong X, Chen X, Liu N, Ding Y, Jin Y. 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 2011; 29(11): 1804–1816

DOI PMID

5
Chen FM, Jin Y. Periodontal tissue engineering and regeneration: current approaches and expanding opportunities. Tissue Eng Part B Rev 2010; 16(2): 219–255

DOI PMID

6
Mooney DJ, Vandenburgh H. Cell delivery mechanisms for tissue repair. Cell Stem Cell 2008; 2(3): 205–213

DOI PMID

7
Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA 2000; 97(25): 13625–13630

DOI PMID

8
Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, Shi S. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci USA 2003; 100(10): 5807–5812

DOI PMID

9
Yasui T, Mabuchi Y, Toriumi H, Ebine T, Niibe K, Houlihan DD, Morikawa S, Onizawa K, Kawana H, Akazawa C, Suzuki N, Nakagawa T, Okano H, Matsuzaki Y. Purified human dental pulp stem cells promote osteogenic regeneration. J Dent Res 2016; 95(2): 206–214

DOI PMID

10
Carinci F, Papaccio G, Laino G, Palmieri A, Brunelli G, D'Aquino R, Graziano A, Lanza V, Scapoli L, Martinelli M, Pezzetti F. Comparison between genetic portraits of osteoblasts derived from primary cultures and osteoblasts obtained from human pulpar stem cells. J Craniofac Surg 2008;19(3):616–625; discussion 626–627

DOI

11
Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S, Smith AJ, Nör JE. Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod 2008; 34(8): 962–969

DOI PMID

12
Telles PD, Machado MA, Sakai VT, Nör JE. Pulp tissue from primary teeth: new source of stem cells. J Appl Oral Sci 2011; 19(3): 189–194

DOI PMID

13
Rosa V, Zhang Z, Grande RH, Nör JE. Dental pulp tissue engineering in full-length human root canals. J Dent Res 2013; 92(11): 970–975

DOI PMID

14
Yamamoto A, Sakai K, Matsubara K, Kano F, Ueda M. Multifaceted neuro-regenerative activities of human dental pulp stem cells for functional recovery after spinal cord injury. Neurosci Res 2014; 78: 16–20

DOI PMID

15
Wang J, Wang X, Sun Z, Wang X, Yang H, Shi S, Wang S. Stem cells from human-exfoliated deciduous teeth can differentiate into dopaminergic neuron-like cells. Stem Cells Dev 2010; 19(9): 1375–1383

DOI PMID

16
d’Aquino R, De Rosa A, Lanza V, Tirino V, Laino L, Graziano A, Desiderio V, Laino G, Papaccio G. Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes. Eur Cell Mater 2009; 18: 75–83

DOI PMID

17
Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, Young M, Robey PG, Wang CY, Shi S. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 2004; 364(9429): 149–155

DOI PMID

18
Ding G, Liu Y, Wang W, Wei F, Liu D, Fan Z, An Y, Zhang C, Wang S. Allogeneic periodontal ligament stem cell therapy for periodontitis in swine. Stem Cells 2010; 28(10): 1829–1838

DOI PMID

19
Park CH, Rios HF, Jin Q, Sugai JV, Padial-Molina M, Taut AD, Flanagan CL, Hollister SJ, Giannobile WV. Tissue engineering bone-ligament complexes using fiber-guiding scaffolds. Biomaterials 2012; 33(1): 137–145

DOI PMID

20
Wang L, Shen H, Zheng W, Tang L, Yang Z, Gao Y, Yang Q, Wang C, Duan Y, Jin Y. Characterization of stem cells from alveolar periodontal ligament. Tissue Eng Part A 2011; 17(7-8): 1015–1026

DOI PMID

21
Silvério KG, Rodrigues TL, Coletta RD, Benevides L, Da Silva JS, Casati MZ, Sallum EA, Nociti FH Jr. Mesenchymal stem cell properties of periodontal ligament cells from deciduous and permanent teeth. J Periodontol 2010; 81(8): 1207–1215

DOI PMID

22
Tomokiyo A, Maeda H, Fujii S, Wada N, Shima K, Akamine A. Development of a multipotent clonal human periodontal ligament cell line. Differentiation 2008; 76(4): 337–347

DOI PMID

23
Singhatanadgit W, Donos N, Olsen I. Isolation and characterization of stem cell clones from adult human ligament. Tissue Eng Part A 2009; 15(9): 2625–2636

DOI PMID

24
Feng F, Akiyama K, Liu Y, Yamaza T, Wang TM, Chen JH, Wang BB, Huang GT, Wang S, Shi S. Utility of PDL progenitors for in vivo tissue regeneration: a report of 3 cases. Oral Dis 2010; 16(1): 20–28

DOI PMID

25
Kim HS, Kim KH, Kim SH, Kim YS, Koo KT, Kim TI, Seol YJ, Ku Y, Rhyu IC, Chung CP, Lee YM. Immunomodulatory effect of canine periodontal ligament stem cells on allogenic and xenogenic peripheral blood mononuclear cells. J Periodontal Implant Sci 2010; 40(6): 265–270

DOI PMID

26
Iwata T, Yamato M, Zhang Z, Mukobata S, Washio K, Ando T, Feijen J, Okano T, Ishikawa I. Validation of human periodontal ligament-derived cells as a reliable source for cytotherapeutic use. J Clin Periodontol 2010; 37(12): 1088–1099

DOI PMID

27
Chen FM, Gao LN, Tian BM, Zhang XY, Zhang YJ, Dong GY, Lu H, Chu Q, Xu J, Yu Y, Wu RX, Yin Y, Shi S, Jin Y. Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial. Stem Cell Res Ther 2016; 7(1): 33

DOI PMID

28
Yang ZH, Zhang XJ, Dang NN, Ma ZF, Xu L, Wu JJ, Sun YJ, Duan YZ, Lin Z, Jin Y. Apical tooth germ cell-conditioned medium enhances the differentiation of periodontal ligament stem cells into cementum/periodontal ligament-like tissues. J Periodontal Res 2009; 44(2): 199–210

DOI PMID

29
Li B, Sun J, Dong Z, Xue P, He X, Liao L, Yuan L, Jin Y. GCN5 modulates osteogenic differentiation of periodontal ligament stem cells through DKK1 acetylation in inflammatory microenvironment. Sci Rep 2016; 6(1): 26542

DOI PMID

30
Xue P, Li B, An Y, Sun J, He X, Hou R, Dong G, Fei D, Jin F, Wang Q, Jin Y. Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation. Cell Death Differ 2016; 23(11): 1862–1872

DOI PMID

31
Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, Liu H, Gronthos S, Wang CY, Wang S, Shi S. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One 2006; 1(1): e79

DOI PMID

32
Bakopoulou A, Leyhausen G, Volk J, Tsiftsoglou A, Garefis P, Koidis P, Geurtsen W. 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 2011; 56(7): 709–721

DOI PMID

33
Han C, Yang Z, Zhou W, Jin F, Song Y, Wang Y, Huo N, Chen L, Qian H, Hou R, Duan Y, Jin Y. Periapical follicle stem cell: a promising candidate for cementum/periodontal ligament regeneration and bio-root engineering. Stem Cells Dev 2010; 19(9): 1405–1415

DOI PMID

34
Jo YY, Lee HJ, Kook SY, Choung HW, Park JY, Chung JH, Choung YH, Kim ES, Yang HC, Choung PH. Isolation and characterization of postnatal stem cells from human dental tissues. Tissue Eng 2007; 13(4): 767–773

DOI PMID

35
Handa K, Saito M, Tsunoda A, Yamauchi M, Hattori S, Sato S, Toyoda M, Teranaka T, Narayanan AS. Progenitor cells from dental follicle are able to form cementum matrix in vivo. Connect Tissue Res 2002; 43(2-3): 406–408

DOI PMID

36
Luan X, Ito Y, Dangaria S, Diekwisch TG. Dental follicle progenitor cell heterogeneity in the developing mouse periodontium. Stem Cells Dev 2006; 15(4): 595–608

DOI PMID

37
Morsczeck C, Götz W, Schierholz J, Zeilhofer F, Kühn U, Möhl C, Sippel C, Hoffmann KH. Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol 2005; 24(2): 155–165

DOI PMID

38
Handa K, Saito M, Yamauchi M, Kiyono T, Sato S, Teranaka T, Sampath Narayanan A. Cementum matrix formation in vivo by cultured dental follicle cells. Bone 2002; 31(5): 606–611

DOI PMID

39
Guo W, Chen L, Gong K, Ding B, Duan Y, Jin Y. Heterogeneous dental follicle cells and the regeneration of complex periodontal tissues. Tissue Eng Part A 2012; 18(5-6): 459–470

DOI PMID

40
Wu J, Jin F, Tang L, Yu J, Xu L, Yang Z, Wu G, Duan Y, Jin Y. Dentin non-collagenous proteins (dNCPs) can stimulate dental follicle cells to differentiate into cementoblast lineages. Biol Cell 2008; 100(5): 291–302

DOI PMID

41
Kémoun P, Laurencin-Dalicieux S, Rue J, Farges JC, Gennero I, Conte-Auriol F, Briand-Mesange F, Gadelorge M, Arzate H, Narayanan AS, Brunel G, Salles JP. Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro. Cell Tissue Res 2007; 329(2): 283–294

DOI PMID

42
Bai Y, Bai Y, Matsuzaka K, Hashimoto S, Fukuyama T, Wu L, Miwa T, Liu X, Wang X, Inoue T. Cementum- and periodontal ligament-like tissue formation by dental follicle cell sheets co-cultured with Hertwig’s epithelial root sheath cells. Bone 2011; 48(6): 1417–1426

DOI PMID

43
Setzer FC, Kim S. Comparison of long-term survival of implants and endodontically treated teeth. J Dent Res 2014; 93(1): 19–26

DOI PMID

44
Nakashima M, Akamine A. The application of tissue engineering to regeneration of pulp and dentin in endodontics. J Endod 2005; 31(10): 711–718

DOI PMID

45
Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S, Smith AJ, Nör JE. Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod 2008; 34(8): 962–969

DOI PMID

46
Guo W, He Y, Zhang X, Lu W, Wang C, Yu H, Liu Y, Li Y, Zhou Y, Zhou J, Zhang M, Deng Z, Jin Y. The use of dentin matrix scaffold and dental follicle cells for dentin regeneration. Biomaterials 2009; 30(35): 6708–6723

DOI PMID

47
Dissanayaka WL, Zhu L, Hargreaves KM, Jin L, Zhang C. Scaffold-free prevascularized microtissue spheroids for pulp regeneration. J Dent Res 2014; 93(12): 1296–1303

DOI PMID

48
Kelm JM, Fussenegger M. Microscale tissue engineering using gravity-enforced cell assembly. Trends Biotechnol 2004; 22(4): 195–202

DOI PMID

49
Kelm JM, Djonov V, Ittner LM, Fluri D, Born W, Hoerstrup SP, Fussenegger M. Design of custom-shaped vascularized tissues using microtissue spheroids as minimal building units. Tissue Eng 2006; 12(8): 2151–2160

DOI PMID

50
Chen FM, Sun HH, Lu H, Yu Q. Stem cell-delivery therapeutics for periodontal tissue regeneration. Biomaterials 2012; 33(27): 6320–6344

DOI PMID

51
Nishida K, Yamato M, Hayashida Y, Watanabe K, Yamamoto K, Adachi E, Nagai S, Kikuchi A, Maeda N, Watanabe H, Okano T, Tano Y. Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. N Engl J Med 2004; 351(12): 1187–1196

DOI PMID

52
Hoashi T, Matsumiya G, Miyagawa S, Ichikawa H, Ueno T, Ono M, Saito A, Shimizu T, Okano T, Kawaguchi N, Matsuura N, Sawa Y. Skeletal myoblast sheet transplantation improves the diastolic function of a pressure-overloaded right heart. J Thorac Cardiovasc Surg 2009; 138(2): 460–467

DOI PMID

53
Flores MG, Hasegawa M, Yamato M, Takagi R, Okano T, Ishikawa I. Cementum-periodontal ligament complex regeneration using the cell sheet technique. J Periodontal Res 2008; 43(3): 364–371

DOI PMID

54
Iwata T, Yamato M, Tsuchioka H, Takagi R, Mukobata S, Washio K, Okano T, Ishikawa I. Periodontal regeneration with multi-layered periodontal ligament-derived cell sheets in a canine model. Biomaterials 2009; 30(14): 2716–2723

DOI PMID

55
Flores MG, Yashiro R, Washio K, Yamato M, Okano T, Ishikawa I. Periodontal ligament cell sheet promotes periodontal regeneration in athymic rats. J Clin Periodontol 2008; 35(12): 1066–1072

DOI PMID

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