Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model (original) (raw)

Abstract

Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine. Oral functions, including mastication, swallowing and pronunciation, are indispensable for adequate general health, social activity and quality of life 1. These functions are carried out by the teeth, masticatory muscles and temporomandibular joint under the control of the central nervous system 2,3. The tooth is an ectodermal organ whose development is regulated by reciprocal epithelial-mesenchymal interactions, and the tooth comprises both distinctive hard tissue (e.g., enamel, dentin and cementum) and soft connective tissues (e.g., pulp and periodontal ligaments, including peripheral nerve fibres and blood vessels) 4-6. The physiological functions of teeth, such as masticatory potential, response to mechanical stress and perceptive potential for noxious stimuli, are efficiently carried out by the characteristic three-dimensional multicellular structure that establishes functional harmonization with the maxillofacial region 2,3. Tooth loss due to dental caries, periodontal disease and traumatic injury causes fundamental oral and general health problems related to oral function and associated general health issues.

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References (55)

  1. Proffit, W. R., Fields, H. W. & Sarver, D. M. Contemporary orthodontics, 4 th edition. John, D. (ed.) 77-83 (Mosby Elsevier, St. Louis, 2006).
  2. Avery, J. K. Oral development and histology Steele, P. F. (ed.) 225-242 (Thieme Press, New York, 2002).
  3. Dawson, P. E. Functional Occlusion: From TMJ to Smile Design. 18-26 (Mosby Press, Missouri, 2006).
  4. Jussila, M., Juuri, E. & Thesleff, I. Tooth morphogenesis and renewal. Stem Cells in Craniofacial Development and Regeneration Huang, G. T. & Thesleff, I. (ed.) 109-134 (John Wiley & Sons, Inc., Hoboken, 2013).
  5. Tucker, A. & Sharpe, P. The cutting-edge of mammalian development; how the embryo makes teeth. Nature reviews Genetics 5, 499-508 (2004).
  6. Oshima, M. & Tsuji, T. Functional tooth regenerative therapy: tooth tissue regeneration and whole-tooth replacement. Odontology 102, 123-136 (2014).
  7. Rosenstiel, S. F., Land, M. F. & Fujimoto, J. Contemporary fixed prosthodontics, 3 rd edition. John, S. & Penny, R. (ed.) 59-82 (Mosby, St. Louis, 2001).
  8. Pokorny, P. H., Wiens, J. P. & Litvak, H. Occlusion for fixed prosthodontics: a historical perspective of the gnathological influence. J Prosthet Dent. 99, 299-313 (2008).
  9. Brenemark, P. I. & Zarb, G. A. Tissue-integrated prostheses: osseointegration in clinical dentistry. Albrektsson, T. (ed.) 211-232 (Quintessence Publishing Co, Inc, Chicago, 1985).
  10. Burns, D. R., Beck, D. A. & Nelson, S. K. 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 (2003).
  11. Korbling, M. & Estrov, Z. Adult stem cells for tissue repair -a new therapeutic concept? N Engl J Med 349, 570-582 (2003).
  12. Brockes, J. P. & Kumar, A. Appendage regeneration in adult vertebrates and implications for regenerative medicine. Science 310, 1919-1923 (2005).
  13. Watt, F. M. & Hogan, B. L. Out of Eden: stem cells and their niches. Science 287, 1427-1430 (2000).
  14. Langer, R. S. & Vacanti, J. P. Tissue engineering: the challenges ahead. Sci Am 280, 86-89 (1999).
  15. Atala, A. Tissue engineering, stem cells and cloning: current concepts and changing trends. Expert Opin Biol Ther 5, 879-892 (2005).
  16. Copelan, E. A. Hematopoietic stem-cell transplantation. N Engl J Med 354, 1813-1826 (2006).
  17. Nishikawa, S., Goldstein, R. A. & Nierras, C. R. The promise of human induced pluripotent stem cells for research and therapy. Nat Rev Mol Cell Biol 9, 725-729 (2008).
  18. Miyahara, Y. et al. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 12, 459-465 (2006).
  19. Ohashi, K. et al. Engineering functional two-and three-dimensional liver systems in vivo using hepatic tissue sheets. Nat Med 13, 880-885 (2007).
  20. Nakao, K. et al. The development of a bioengineered organ germ method. Nat Methods 4, 227-230 (2007).
  21. Ikeda, E. et al. Fully functional bioengineered tooth replacement as an organ replacement therapy. Proc Natl Acad Sci USA 106, 13475-13480 (2009).
  22. Oshima, M. et al. Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy. PLoS One 6, e21531 (2011).
  23. Toyoshima, K. E. et al. Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches. Nat Commun 3, 784 (2012).
  24. Ogawa, M. et al. Functional salivary gland regeneration by transplantation of a bioengineered organ germ. Nat Commun 4, 2498 (2013).
  25. Volponi, A. A., Pang, Y. & Sharpe, P. T. Stem cell-based biological tooth repair and regeneration. Trends Cell Biol 20, 715-722 (2010).
  26. Lechler, R. I., Sykes, M., Thomson, A. W. & Turka, L. A. Organ transplantation-how much of the promise has been realized? Nat Med 11, 605-613 (2005).
  27. Gridelli, B. & Remuzzi, G. Strategies for making more organs available for transplantation. N Engl J Med 343, 404-410 (2000).
  28. Nankivell, B. J. & Alexander, S. I. Rejection of the kidney allograft. N Engl J Med 363, 1451-1462 (2010).
  29. Wood, K. J. & Goto, R. Mechanisms of rejection: current perspectives. Transplantation 93, 1-10 (2012).
  30. Chinen, J. & Buckley, R. H. Transplantation immunology: solid organ and bone marrow. J Allergy Clin Immunol 125, S324-335 (2010).
  31. Sanchez-Fueyo, A. & Strom, T. B. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs. Gastroenterology 140, 51-64 (2011).
  32. Tsukiboshi, M. Autogenous tooth transplantation: a reevaluation. Int J Periodontics Restorative Dent 13, 120-149 (1993).
  33. Bauss, O., Engelke, W., Fenske, C., Schilke, R. & Schwestka-Polly, R. Autotransplantation of immature third molars into edentulous and atrophied jaw sections. Int J Oral Maxillofac Surg 33, 558-563 (2004).
  34. Lai, F. S. Autotransplantation of an unerupted wisdom tooth germ without its follicle immediately after removal of an impacted mandibular second molar: a case report. J Can Dent Assoc 75, 205-208 (2009).
  35. Gerard, E., Membre, H., Gaudy, J. F., Mahler, P. & Bravetti, P. Functional fixation of autotransplanted tooth germs by using bioresorbable membranes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 94, 667-672 (2002).
  36. Shimono, M. et al. Regulatory mechanisms of periodontal regeneration. Microsc Res Tech 60, 491-502 (2003).
  37. Hu, B. et al. Tissue engineering of tooth crown, root, and periodontium. Tissue Eng 12, 2069-2075 (2006).
  38. Yamamoto, H., Kim, E. J., Cho, S. W. & Jung, H. S. Analysis of tooth formation by reaggregated dental mesenchyme from mouse embryo. J Electron Microsc (Tokyo) 52, 559-566 (2003).
  39. Young, C. S. et al. Tissue engineering of complex tooth structures on biodegradable polymer scaffolds. J Dent Res 81, 695-700 (2002).
  40. Duailibi, M. T. et al. Bioengineered teeth from cultured rat tooth bud cells. J Dent Res 83, 523-528 (2004).
  41. Yelick, P. C. & Vacanti, J. P. Bioengineered teeth from tooth bud cells. Dent Clin North Am 50, 191-203, viii (2006).
  42. Honda, M. J., Tsuchiya, S., Sumita, Y., Sagara, H. & Ueda, M. The sequential seeding of epithelial and mesenchymal cells for tissue- engineered tooth regeneration. Biomaterials 28, 680-689 (2007).
  43. Duailibi, S. E. et al. Bioengineered dental tissues grown in the rat jaw. J Dent Res, 87(8), 745-750 (2008).
  44. Zhang, W., Vázquez, B. & Yelick, P. C. Bioengineered postnatal recombinant tooth bud models. J Tissue Eng Regen Med, doi: 10.1002/ term.1962 (2014).
  45. Isogawa, N. et al. The induction of enamel and dentin complexes by subcutaneous implantation of reconstructed human and murine tooth germ elements. Arch Histol Cytol 67, 65-77 (2004).
  46. Yan, X. et al. iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev. 19, 469-480 (2010).
  47. Egusa, H., Sonoyama, W., Nishimura, M., Atsuta, I. & Akiyama, K. Stem cells in dentistry-part I: stem cell sources. J Prosthodont Res. 56, 151-165 (2012).
  48. Egusa, H., Sonoyama, W., Nishimura, M., Atsuta, I. & Akiyama, K. Stem cells in dentistry-Part II: Clinical applications. J Prosthodont Res. 56, 229-248 (2012).
  49. Tan, J. et al. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA 307, 1169-1177 (2012).
  50. Quarto, R. et al. Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 344, 385-386 (2001).
  51. Morizane, A. et al. Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate. Stem Cell Reports 1, 283-292 (2013).
  52. Ishida, K. et al. 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, 455-61 (2011).
  53. Egusa, H. et al. Gingival fibroblasts as a promising source of induced pluripotent stem cells. PLoS One 5, e12743 (2010).
  54. Arakaki, M. et al. Role of epithelial-stem cell interactions during dental cell differentiation. J Biol Chem. 287, 10590-10601 (2012).
  55. Otsu, K. et al. Differentiation of induced pluripotent stem cells into dental mesenchymal cells. Stem Cells Dev. 21, 1156-1164 (2012).