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EPMA Journal

pp 1–12 | Cite as

Stem cells and tooth regeneration: prospects for personalized dentistry

  • Mahmood S. Mozaffari
  • Golnaz Emami
  • Hesam Khodadadi
  • Babak Baban
Review
  • 3 Downloads

Abstract

Over the last several decades, a wealth of information has become available regarding various sources of stem cells and their potential use for regenerative purposes. Given the intense debate regarding embryonic stem cells, much of the focus has centered around application of adult stem cells for regenerative engineering along with other relevant aspects including use of growth factors and scaffolding materials. The more recent discovery of tooth-derived stem cells has sparked much interest in their application to regenerative dentistry to treat and alleviate the most prevalent oral diseases—i.e., dental caries and periodontal diseases. Also exciting is the advent of induced pluripotent stem cells, which provides the means of using patient-derived somatic cells for their creation, and their eventual application for generation of the dental complex. Thus, evolving developments in the field of regenerative dentistry indicate the prospect of constructing “custom-made” tooth and supporting structures thereby fostering the realization of “personalized dentistry.” On the other hand, others have explored the possibility of augmenting endogenous regenerative capacity through utilization of small molecules to regulate molecular signaling mechanisms that mediate regeneration of tooth structure. This review is focused on these aspects of regenerative dentistry in view of their relevance to personalized dentistry.

Keywords

Stem cells Molecular mechanisms Dentin/pulp complex Tissue repair Tooth regeneration Personalized dentistry Predictive preventive personalized medicine (PPPM) 

Notes

Compliance and ethical standards

Conflict of interest

Authors declare that they have no competing interest.

Consent for publication

Not applicable.

Ethical approval

This submission does not involve the use of human subjects.

Human and animal rights

No experiments have been performed using patients and/or animals.

References

  1. 1.
    World Health Organization. Oral disease burdens and common risk factors. 2018. http://www.who.int/oral_health/disease_burden/global/en/. Accessed 25 Dec 2018.
  2. 2.
    Petersen PE, Ogawa H. The global burden of periodontal disease: towards integration with chronic disease prevention and control. Periodontol. 2012;60(1):15–39.  https://doi.org/10.1111/j.1600-0757.2011.00425.x. CrossRefGoogle Scholar
  3. 3.
    Patel R. The state of oral health in Europe. Report Commissioned by the Platform for Better Oral Health in Europe. 2012. http://www.oralhealthplatform.eu/wp-content/uploads/2015/09/Report-the-State-of-Oral-Health-in-Europe.pdf. Accessed 25 Dec 2018.
  4. 4.
    Centers for Disease Control and Prevention. Health, United States, 2016. https://www.cdc.gov/nchs/data/hus/hus16.pdf#060. Accessed 25 Dec 2018.
  5. 5.
    World Health Organization. Oral health: data and statics. http://www.euro.who.int/en/health-topics/disease-prevention/oral-health/data-and-statistics. Accessed 25 Dec 2018.
  6. 6.
    Centers for Disease Control and Prevention. Periodontal disease. https://www.cdc.gov/oralhealth/periodontal_disease/index.htm. Accessed 25 Dec 2018.
  7. 7.
    Bartold MP, Mariotti A. The future of periodontal-systemic associations: raising the standards. Curr Oral Health Rep. 2017;4(3):258–62.  https://doi.org/10.1007/s40496-017-0150-2.CrossRefGoogle Scholar
  8. 8.
    Hirschfeld J, Kawai T. Oral inflammation and bacteremia: implications for chronic and acute systemic diseases involving major organs. Cardiovasc Hematol Disord Drug Targets. 2015;15(1):70–84.  https://doi.org/10.2174/1871529X15666150108115241.CrossRefPubMedGoogle Scholar
  9. 9.
    Golubnitschaja O, Costigliola V, EPMA. General report & recommendations in predictive, preventive and personalised medicine 2012: white paper of the European Association for Predictive, Preventive and Personalised Medicine. EPMA J. 2012;3(1):14.  https://doi.org/10.1186/1878-5085-3-14.
  10. 10.
    Golubnitschaja O, Costigliola V, Grech G. EPMA World Congress: Traditional forum in predictive, preventive and personalised medicine for multi-professional consideration and consolidation. EPMA J. 2017;8(Suppl 1):1–54.  https://doi.org/10.1007/s13167-017-0108-4. CrossRefGoogle Scholar
  11. 11.
    Balic A. Biology explaining tooth repair and regeneration: a mini-review. Gerontology. 2018;64(4):382–8.  https://doi.org/10.1159/000486592.CrossRefPubMedGoogle Scholar
  12. 12.
    Li J, Parada C, Chai Y. Cellular and molecular mechanisms of tooth root development. Development. 2017;144(3):374–84.  https://doi.org/10.1242/dev.137216.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Amrollahi P, Shah B, Seifi A, Tayebi L. Recent advancements in regenerative dentistry: a review. Mater Sci Eng C Mater Biol Appl. 2016;69:1383–90.  https://doi.org/10.1016/j.msec.2016.08.045.CrossRefPubMedGoogle Scholar
  14. 14.
    National Institutes of Health. Stem cells information. Stem Cell Basics IV. https://stemcells.nih.gov/info/basics/4.htm. Accessed 25 Dec 2018.
  15. 15.
    National Institutes of Health. Stem cells information. Stem Cell Basics I. https://stemcells.nih.gov/info/basics/1.htm. Accessed 25 Dec 2018.
  16. 16.
    Tzahor E, Poss KD. Cardiac regeneration strategies: staying young at heart. Science. 2017;356(6342):1035–9.  https://doi.org/10.1126/science.aam5894.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Egawa N, Takase H, Josephine L, Takahashi R, Arai K. Clinical application of oligodendrocyte precursor cells for cell-based therapy. Brain Circ. 2016;2(3):121–5.  https://doi.org/10.4103/2394-8108.192515.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Huang L, Zhang L. Neural stem cell therapies and hypoxic-ischemic brain injury. Prog Neurobiol. 2018.  https://doi.org/10.1016/j.pneurobio.2018.05.004.
  19. 19.
    Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol. 1962;10:622–40.PubMedGoogle Scholar
  20. 20.
    Gurdon JB. Nuclear transplantation, the conservation of the genome, and prospects for cell replacement. FEBS J. 2017;284(2):211–7.  https://doi.org/10.1111/febs.13988.CrossRefPubMedGoogle Scholar
  21. 21.
    Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.  https://doi.org/10.1016/j.cell.2006.07.024.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Yu J, Vodyanik MA, Smuga Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20.  https://doi.org/10.1126/science.1151526.CrossRefPubMedGoogle Scholar
  23. 23.
    Cai J, Zhang Y, Liu P, Chen S, Wu X, Sun Y, et al. Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells. Cell Regen (Lond). 2013;2(1):6.  https://doi.org/10.1186/2045-9769-2-6. CrossRefGoogle Scholar
  24. 24.
    Yan X, Qin H, Qu C, Tuan RS, Shi S, Huang GT. iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev. 2010;19(4):469–80.  https://doi.org/10.1089/scd.2009.0314.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Wen W, Zhang JP, Chen W, Arakaki C, Li X, Baylink D, et al. Generation of integration-free induced pluripotent stem cells from human peripheral blood mononuclear cells using episomal vectors. J Vis Exp. 2017;119.  https://doi.org/10.3791/55091.
  26. 26.
    Durcova-Hills G. Induced reprogramming of human somatic cells into pluripotency: a new way how to generate pluripotent stem cells. Differentiation. 2008;76(4):323–5.  https://doi.org/10.1111/j.1432-0436.2008.00266.x.CrossRefPubMedGoogle Scholar
  27. 27.
    Bang JS, Choi NY, Lee M, Ko K, Lee HJ, Park YS, et al. Optimization of episomal reprogramming for generation of human induced pluripotent stem cells from fibroblasts. Anim Cells Syst. 2018;22(2):132–9.  https://doi.org/10.1080/19768354.2018.1451367.CrossRefGoogle Scholar
  28. 28.
    Lee YM, Zampieri BL, Scott-McKean JJ, Johnson MW, Costa ACS. Generation of integration-free induced pluripotent stem cells from urine-derived cells isolated from individuals with down syndrome. Stem Cells Transl Med. 2017;6(6):1465–76.  https://doi.org/10.1002/sctm.16-0128.CrossRefGoogle Scholar
  29. 29.
    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 U S A. 2000;97(25):13625–30.  https://doi.org/10.1073/pnas.240309797.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Tatullo M, Marrelli M, Shakesheff KM, White LJ. Dental pulp stem cells: function, isolation and applications in regenerative medicine. J Tissue Eng Regen Med. 2015;9(11):1205–16.  https://doi.org/10.1002/term.1899.CrossRefPubMedGoogle Scholar
  31. 31.
    Hu L, Liu Y, Wang S. Stem cell-based tooth and periodontal regeneration. Oral Dis. 2018;24(5):696–705.  https://doi.org/10.1111/odi.12703.CrossRefPubMedGoogle Scholar
  32. 32.
    Miran S, Mitsiadis TA, Pagella P. Innovative dental stem cell-based research approaches: the future of dentistry. Stem Cells Int. 2016;2016:7231038.  https://doi.org/10.1155/2016/7231038.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Park YJ, Cha S, Park YS. Regenerative applications using tooth derived stem cells in other than tooth regeneration: a literature review. Stem Cells Int. 2016;2016:9305986.  https://doi.org/10.1155/2016/9305986.CrossRefPubMedGoogle Scholar
  34. 34.
    Zhai Q, Dong Z, Wang W, Li B, Jin Y. Dental stem cell and dental tissue regeneration. Front Med. 2018.  https://doi.org/10.1007/s11684-018-0628-x.
  35. 35.
    Chavez MG, Hu J, Seidel K, Li C, Jheon A, Naveau A, et al. Isolation and culture of dental epithelial stem cells from the adult mouse incisor. J Vis Exp. 2014;87.  https://doi.org/10.3791/51266.
  36. 36.
    Yu T, Volponi AA, Babb R, An Z, Sharpe PT. Stem cells in tooth development, growth, repair, and regeneration. Curr Top Dev Biol. 2015;115:187–212.  https://doi.org/10.1016/bs.ctdb.2015.07.010.CrossRefPubMedGoogle Scholar
  37. 37.
    Zhang Y, Li Y, Shi R, Zhang S, Liu H, Zheng Y, et al. Generation of tooth-periodontium complex structures using high-odontogenic potential dental epithelium derived from mouse embryonic stem cells. Stem Cell Res Ther. 2017;8(1):141.  https://doi.org/10.1186/s13287-017-0583-5. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kollar EJ, Baird GR. Tissue interactions in embryonic tooth germs. I. Reorganization of the dental epithelium during tooth germ reconstruction. J Embryol Exp Morphol. 1970;24(1):173–86.PubMedGoogle Scholar
  39. 39.
    Kollar EJ, Baird GR. Tissue interactions in embryonic mouse tooth germs. II. The inductive role of dental papilla. J Embryol Exp Morphol. 1970;24(1):173–86.PubMedGoogle Scholar
  40. 40.
    Komine A, Suenaga M, Nakao K, Tsuji T, Tomooka Y. Tooth regeneration from newly established cell lines from a molar tooth germ epithelium. Biochem Biophys Res Commun. 2007;355(3):758–63.  https://doi.org/10.1016/j.bbrc.2007.02.039.CrossRefPubMedGoogle Scholar
  41. 41.
    Nakao K, Morita R, Saji Y, Ishida K, Tomita Y, Ogawa M, et al. The development of a bioengineered organ germ method. Nat Methods. 2007;4(3):227–30.  https://doi.org/10.1038/nmeth1012.CrossRefPubMedGoogle Scholar
  42. 42.
    Ikeda E, Morita R, Nakao K, Ishida K, Nakamura T, Takano-Yamamoto T, et al. Fully functional bioengineered tooth replacement as an organ replacement therapy. Proc Natl Acad Sci U S A. 2009;106(32):13475–80.  https://doi.org/10.1073/pnas.0902944106.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Oshima M, Mizuno M, Imamura A, Ogawa M, Yasukawa M, Yamazaki H, et al. Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy. PLoS One. 2011;6(7):e21531.  https://doi.org/10.1371/journal.pone.0021531.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Xuan K, Li B, Guo H, Sun W, Kou X, He X, et al. Decidous autologous tooth stem cell regenerate dental pulp after implantation into injured teeth. Sci Transl Med. 2018;10(455):eaaf3227.  https://doi.org/10.1126/scitranslmed.aaf3227.CrossRefPubMedGoogle Scholar
  45. 45.
    Habelitz S, Marshall SJ, Marshall GWJ, Balooch M. Mechanical properties of human dental enamel on the nanometre scale. Arch Oral Biol. 2001;46(2):173–83.  https://doi.org/10.1016/S0003-9969(00)00089-3.CrossRefPubMedGoogle Scholar
  46. 46.
    Jayasudha, Baswaraj, Navin HK, Prasanna KB. Enamel regeneration—current progress and challenges. J Clin Diagn Res. 2014;8(9):ZE06–9.  https://doi.org/10.7860/JCDR/2014/10231.4883.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Yamagishi K, Onuma K, Suzuki T, Okada F, Tagami J, Otsuki M, et al. A synthetic enamel for rapid tooth repair. Nature. 2005;433(7028):819.  https://doi.org/10.1038/433819a. CrossRefPubMedGoogle Scholar
  48. 48.
    Yin Y, Yun S, Fang J, Chen H. Chemical regeneration of human tooth enamel under near-physiological conditions. Chem Commun (Camb). 2009;(39):5892–4.  https://doi.org/10.1039/b911407f.
  49. 49.
    Palmer LC, Newcomb CJ, Kaltz SR, Spoerke ED, Stupp SI. Biomimetic systems for hydroxyapatite mineralization inspired by bone and enamel. Chem Rev. 2008;108(11):4754–83.  https://doi.org/10.1021/cr8004422.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Ruan Q, Zhang Y, Yang X, Nutt S, Moradian-Oldak J. An amelogenin chitosan matrix promotes assembly of an enamel-like layer with a dense interface. Acta Biomater. 2013;9(7):7289–97.  https://doi.org/10.1016/j.actbio.2013.04.004.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Elsharkawy S, Al-Jawad M, Pantano MF, Tejeda-Montes E, Mehta K, Jamal H, et al. Protein disorder–order interplay to guide the growth of hierarchical mineralized structures. Nat Commun. 2018;9(1):2145.  https://doi.org/10.1038/s41467-018-04319-0. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Hashemi-Beni B, Khoroushi M, Foroughi MR, Karbasi S, Khademi AA. Tissue engineering: dentin–pulp complex regeneration approaches (a review). Tissue Cell. 2017;49(5):552–64.  https://doi.org/10.1016/j.tice.2017.07.002.CrossRefPubMedGoogle Scholar
  53. 53.
    Itoh Y, Sasaki JI, Hashimoto M, Katata C, Hayashi M, Imazato S. Pulp regeneration by 3-dimensional dental pulp stem cell constructs. J Dent Res. 2018;97(10):1137–43.  https://doi.org/10.1177/0022034518772260.CrossRefPubMedGoogle Scholar
  54. 54.
    Smith EE, Angstadt S, Monteiro N, Zhang W, Khademhosseini A, Yelick PC. Bioengineered tooth buds exhibit features of natural tooth buds. J Dent Res. 2018;97(10):1144–51.  https://doi.org/10.1177/0022034518779075.CrossRefPubMedGoogle Scholar
  55. 55.
    Zhang W, Vazquez B, Oreadi D, Yelick PC. Decellularized tooth bud scaffolds for tooth regeneration. J Dent Res. 2017;96(5):516–23.  https://doi.org/10.1177/0022034516689082.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Oshima M, Tsuji T. Functional tooth regenerative therapy: tooth tissue regeneration and whole-tooth replacement. Odontology. 2014;102(2):123–36.  https://doi.org/10.1007/s10266-014-0168-z.CrossRefPubMedGoogle Scholar
  57. 57.
    Kitamura C, Nishihara T, Terashita M, Tabata Y, Washio A. Local regeneration of dentin-pulp complex using controlled release of fgf-2 and naturally derived sponge-like scaffolds. Int J Dent. 2012;2012:190561.  https://doi.org/10.1155/2012/190561.CrossRefPubMedGoogle Scholar
  58. 58.
    Rodas-Junco BA, Canul-Chan M, Rojas-Herrera RA, De-la-Peña C, Nic-Can GI. Stem cells from dental pulp: what epigenetics can do with your tooth. Front Physiol. 2017;8:999.  https://doi.org/10.3389/fphys.2017.00999.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Wang HS, Pei F, Chen Z, Zhang L. Increased apoptosis of inflamed odontoblasts is associated with CD47 loss. J Dent Res. 2016;95(6):697–703.  https://doi.org/10.1177/0022034516633639.CrossRefPubMedGoogle Scholar
  60. 60.
    Li M, Sun X, Ma L, Jin L, Zhang W, Xiao M, et al. SDF-1/CXCR4 axis induces human dental pulp stem cell migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways. Sci Rep. 2017;7:40161.  https://doi.org/10.1038/srep40161.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Neves VCM, Babb R, Chandrasekaran D, Sharpe PT. Promotion of natural tooth repair by small molecule GSK3 antagonists. Sci Rep. 2017;7:39654.  https://doi.org/10.1038/srep39654.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Neves VCM, Sharpe PT. Regulation of reactionary dentine formation. J Dent Res. 2018;97(4):416–22.  https://doi.org/10.1177/0022034517743431.CrossRefPubMedGoogle Scholar

Copyright information

© European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2019

Authors and Affiliations

  1. 1.Department of Oral Biology and Diagnostic Sciences; CL-2134, Dental College of GeorgiaAugusta UniversityAugustaUSA

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