Abstract
Dental problems caused by dental caries, periodontal disease and tooth injury compromise the oral and general health issues. Current advances for the development of regenerative therapy have been influenced by our understanding of embryonic development, stem cell biology, and tissue engineering technology. Tooth regenerative therapy for tooth tissue repair and whole tooth replacement is currently expected a novel therapeutic concept with the full recovery of tooth physiological functions. Dental stem cells and cell-activating cytokines are thought to be candidate approach for tooth tissue regeneration because they have the potential to differentiate into tooth tissues in vitro and in vivo. Whole tooth replacement therapy is considered to be an attractive concept for next generation regenerative therapy as a form of bioengineered organ replacement. For realization of whole tooth regeneration, we have developed a novel three-dimensional cell manipulation method designated the “organ germ method”. This method involves compartmentalisation of epithelial and mesenchymal cells at a high cell density to mimic multicellular assembly conditions and epithelial-mesenchymal interactions in organogenesis. The bioengineered tooth germ generates a structurally correct tooth in vitro, and erupted successfully with correct tooth structure when transplanted into the oral cavity. We have ectopically generated a bioengineered tooth unit composed of a mature tooth, periodontal ligament and alveolar bone, and that tooth unit was engrafted into an adult jawbone through bone integration. Bioengineered teeth were also able to perform physiological tooth functions such as mastication, periodontal ligament function and response to noxious stimuli. In this review, we describe recent findings and technologies underpinning whole tooth regenerative therapy.
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References
Arakaki M, Ishikawa M, Nakamura T et al (2012) Role of epithelial-stem cell interactions during dental cell differentiation. J Biol Chem 287:10590–10601
Atala A (2005) Tissue engineering, stem cells and cloning: current concepts and changing trends. Expert Opin Biol Ther 5:879–892
Avery JK (2002) Oral development and histology. Thieme Press, New York
Bei M (2009) Molecular genetics of tooth development. Curr Opin Genet Dev 19:504–510
Brenemark PI, Zarb GA (1985) Tissue-integrated prostheses. In: Albrektsson T (ed) Osseointegration in clinical dentistry. Quintessence Pub Co Press, Berlin, pp 211–232
Brockes JP, Kumar A (2005) Appendage regeneration in adult vertebrates and implications for regenerative medicine. Science 310:1919–1923
Burns DR, Beck DA, Nelson SK (2003) A review of selected dental literature on contemporary provisional fixed prosthodontic treatment: report of the Committee on Research in Fixed Prosthodontics of the Academy of Fixed Prosthodontics. J Prosthet Dent 90:474–497
Cai J, Cho SW, Kim JY et al (2007) Patterning the size and number of tooth and its cusps. Dev Biol 304:499–507
Cao Y, Vacanti JP, Paige KT et al (1997) Transplantation of chondrocytes utilizing a polymer-cell construct to produce tissue-engineered cartilage in the shape of a human ear. Plast Reconstr Surg 100:297–304
Caplan AI, Bruder SP (2001) Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends Mol Med 7:259–264
Copelan EA (2006) Hematopoietic stem-cell transplantation. N Engl J Med 354:1813–1826
Dawson PE (2006) Functional occlusion: from TMJ to smile design. Mosby, St. Louis
Duailibi MT, Duailibi SE, Young CS et al (2004) Bioengineered teeth from cultured rat tooth bud cells. J Dent Res 83:523–528
Duailibi SE, Duailibi MT, Vacanti JP et al (2006) Prospects for tooth regeneration. Periodontol 2000 41:177–187
Egusa H, Okita K, Kayashima H et al (2010) Gingival fibroblasts as a promising source of induced pluripotent stem cells. PLoS One 5:e12743
Egusa H, Sonoyama W, Nishimura M et al (2012) Stem cells in dentistry–part I: stem cell sources. J Prosthodont Res 56:151–165
Egusa H, Sonoyama W, Nishimura M et al (2013) Stem cells in dentistry–part II: clinical applications. J Prosthodont Res 56:229–248
Eiraku M, Takata N, Ishibashi H et al (2011) Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472:51–56
Foster BL, Popowics TE, Fong HK et al (2007) Advances in defining regulators of cementum development and periodontal regeneration. Curr Top Dev Biol 78:47–126
Fukumoto S, Yamada Y (2005) Review: extracellular matrix regulates tooth morphogenesis. Connect Tissue Res 46:220–226
Gridelli B, Remuzzi G (2000) Strategies for making more organs available for transplantation. N Engl J Med 343:404–410
Gronthos S, Mankani M, Brahim J et al (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A 97:13625–13630
Honda M, Morikawa N, Hata K et al (2003) Rat costochondral cell characteristics on poly (L-lactide-co-epsilon-caprolactone) scaffolds. Biomaterials 24:3511–3519
Honda MJ, Tsuchiya S, Sumita Y et al (2007) The sequential seeding of epithelial and mesenchymal cells for tissue-engineered tooth regeneration. Biomaterials 28:680–689
Hu B, Nadiri A, Kuchler-Bopp S et al (2006) Tissue engineering of tooth crown, root, and periodontium. Tissue Eng 12:2069–2075
Huang GT, Gronthos S, Shi S (2009) Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 88:792–806
Ikeda E, Tsuji T (2008) Growing bioengineered teeth from single cells: potential for dental regenerative medicine. Expert Opin Biol Ther 8:735–744
Ikeda E, Morita R, Nakao K et al (2009) Fully functional bioengineered tooth replacement as an organ replacement therapy. Proc Natl Acad Sci U S A 106:13475–13480
Ishida K, Murofushi M, Nakao K et al (2011) The regulation of tooth morphogenesis is associated with epithelial cell proliferation and the expression of sonic hedgehog through epithelial-mesenchymal interactions. Biochem Biophys Res Commun 405:455–461
Iwatsuki S, Honda MJ, Harada H et al (2006) Cell proliferation in teeth reconstructed from dispersed cells of embryonic tooth germs in a three-dimensional scaffold. Eur J Oral Sci 114:310–317
Jussila M, Juuri E, Thesleff I (2013) Tooth morphogenesis and renewal. Stem cells in craniofacial development and regeneration. Wiley-Blackwell, Hoboken, New Jersey, pp 109–134
Kjaer M, Beyer N, Secher NH (1999) Exercise and organ transplantation. Scand J Med Sci Sports 9:1–14
Korbling M, Estrov Z (2003) Adult stem cells for tissue repair – a new therapeutic concept? N Engl J Med 349:570–582
Langer RS, Vacanti JP (1999) Tissue engineering: the challenges ahead. Sci Am 280:86–89
Lindhe J, Lang NP, Karring T (2008) Clinical periodontology and implant dentistry, 5th edn. Blackwell Munksgaard, Oxford, UK
Lindvall O, Kokaia Z (2006) Stem cells for the treatment of neurological disorders. Nature 441:1094–1096
Luukko K, Kvinnsland IH, Kettunen P (2005) Tissue interactions in the regulation of axon pathfinding during tooth morphogenesis. Dev Dyn 234:482–488
Mantesso A, Sharpe P (2009) Dental stem cells for tooth regeneration and repair. Expert Opin Biol Ther 9:1143–1154
Miura M, Gronthos S, Zhao M et al (2003) SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 100:5807–5812
Nakao K, Morita R, Saji Y et al (2007) The development of a bioengineered organ germ method. Nat Methods 4:227–230
Nakatomi M, Wang XP, Key D et al (2010) Genetic interactions between Pax9 and Msx1 regulate lip development and several stages of tooth morphogenesis. Dev Biol 340:438–449
Nanci A (2012) Ten Cate’s oral histology: development, structure, and function. Mosby Press, St. Louis
Ohazama A, Modino SA, Miletich I et al (2004) Stem-cell-based tissue engineering of murine teeth. J Dent Res 83:518–522
Oshima M, Mizuno M, Imamura A et al (2011) Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy. PLoS One 6:e21531
Otsu K, Kishigami R, Oikawa-Sasaki A et al (2012) Differentiation of induced pluripotent stem cells into dental mesenchymal cells. Stem Cells Dev 21:1156–1164
Pokorny PH, Wiens JP, Litvak H (2008) Occlusion for fixed prosthodontics: a historical perspective of the gnathological influence. J Prosthet Dent 99:299–313
Proffit WR, Fields HW Jr, Sarver DM (2004) Contemporary orthodontics. Mosby Press, St. Louis, pp 78–83
Purnell B (2008) New release: the complete guide to organ repair. Introduction. Science 322:1489
Quarto R, Mastrogiacomo M, Cancedda R et al (2001) Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 344:385–386
Rosenstiel SF, Land MF, Fujimoto J (2001) Contemporary fixed prosthodontics. Mosby Press, Missouri, pp 209–430
Sasai Y (2013) Next-generation regenerative medicine: organogenesis from stem cells in 3D culture. Cell Stem Cell 12:520–530
Sedohara A, Komazaki S, Asashima M (2003) In vitro induction and transplantation of eye during early Xenopus development. Dev Growth Differ 45:463–471
Segers VF, Lee RT (2008) Stem-cell therapy for cardiac disease. Nature 451:937–942
Seo BM, Miura M, Gronthos S et al (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364:149–155
Shackleton M, Vaillant F, Simpson KJ et al (2006) Generation of a functional mammary gland from a single stem cell. Nature 439:84–88
Sharpe PT, Young CS (2005) Test-tube teeth. Sci Am 293:34–41
Song Y, Zhang Z, Yu X et al (2006) Application of lentivirus-mediated RNAi in studying gene function in mammalian tooth development. Dev Dyn 235:1334–1344
Sonoyama W, Liu Y, Yamaza T et al (2008) Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod 34:166–171
Suga H, Kadoshima T, Minaguchi M et al (2011) Self-formation of functional adenohypophysis in three-dimensional culture. Nature 480:57–62
Sumita Y, Honda MJ, Ohara T et al (2006) Performance of collagen sponge as a 3-D scaffold for tooth-tissue engineering. Biomaterials 27:3238–3248
Thesleff I (2003) Epithelial-mesenchymal signalling regulating tooth morphogenesis. J Cell Sci 116:1647–1648
Tsukiboshi M (1993) Autogenous tooth transplantation: a reevaluation. Int J Periodontics Restorative Dent 13:120–149
Tucker A, Sharpe P (2004) The cutting-edge of mammalian development; how the embryo makes teeth. Nat Rev Genet 5:499–508
Tyler D, Baker NE (2003) Size isn’t everything. Bioessays 25:5–8
Volponi AA, Pang Y, Sharpe PT (2010) Stem cell-based biological tooth repair and regeneration. Trends Cell Biol 20:715–722
Wang X et al (2003) The origin and liver repopulating capacity of murine oval cells. Proc Natl Acad Sci U S A 100:11881–11888
Watt FM, Hogan BL (2000) Out of Eden: stem cells and their niches. Science 287:1427–1430
Wise GE, King GJ (2008) Mechanisms of tooth eruption and orthodontic tooth movement. J Dent Res 87:414–434
Wise GE, Frazier-Bowers S, D’Souza RN (2002) Cellular, molecular, and genetic determinants of tooth eruption. Crit Rev Oral Biol Med 13:323–334
Yamamoto H, Kim EJ, Cho SW et al (2003) Analysis of tooth formation by reaggregated dental mesenchyme from mouse embryo. J Electron Microsc 52:559–566
Yan X, Qin H, Qu C et al (2010) iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev 19:469–480
Yang Z, Jin F, Zhang X et al (2009) Tissue engineering of cementum/periodontal-ligament complex using a novel three-dimensional pellet cultivation system for human periodontal ligament stem cells. Tissue Eng Part C Methods 15:571–581
Yelick PC, Vacanti JP (2006) Bioengineered teeth from tooth bud cells. Dent Clin N Am 50:191–203
Yen AH, Sharpe PT (2008) Stem cells and tooth tissue engineering. Cell Tissue Res 331:359–372
Young CS, Terada S, Vacanti JP et al (2002) Tissue engineering of complex tooth structures on biodegradable polymer scaffolds. J Dent Res 81:695–700
Zheng Y, Du X, Wang W et al (2005) Organogenesis from dissociated cells: generation of mature cycling hair follicles from skin-derived cells. J Invest Dermatol 124:867–876
Acknowledgements
This work was partially supported by Health and Labour Sciences Research Grants from the Ministry of Health, Labour, and Welfare (no. 21040101) to Akira Yamaguchi (Tokyo Medical and Dental University), a Grant-in-Aid for Scientific Research (A) (no. 20249078) to T. Tsuji (2008–2010) and a Grant-in-Aid for Young Scientists (B) to M. Oshima from the Ministry of Education, Culture, Sports and Technology, Japan. This work was also partially supported by Organ Technologies Inc.
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Oshima, M., Tsuji, T. (2015). Whole Tooth Regeneration as a Future Dental Treatment. In: Bertassoni, L., Coelho, P. (eds) Engineering Mineralized and Load Bearing Tissues. Advances in Experimental Medicine and Biology, vol 881. Springer, Cham. https://doi.org/10.1007/978-3-319-22345-2_14
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DOI: https://doi.org/10.1007/978-3-319-22345-2_14
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