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Japanese Scientists Develop Tooth Structures in Mice from Single Cells

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Overview

Researchers from the Tokyo University of Science are reporting the development of structurally correct tooth structures from cultured single-cell specimens as a replacement for natural teeth in mice. The study was published in the online journal Nature Methods ,¹ and its release attracted news coverage from Reuters ,² HealthDay , ³ New Scientist ⁴ and Technology Review . ⁵

In the study, the researchers cultured cells from the mesenchymal and epithelial tissues of 8-week-old mice and injected the cells into collagen to form a bioengineered tooth germ. The reconstituted tooth germ was developed over two weeks either by in vitro organ culture or by in vivo transplantation into the adult mice (in subrenal capsules). Using either method, the researchers found the bioengineered tooth germ developed with correctly placed mineralized tissue and cell types.

The researchers also examined if the bioengineered tooth germ or the developing tooth (cultivated in vivo after implantation of the subrenal capsule) could be successfully transplanted and redevelop in a tooth cavity left after extracting an incisor from an adult mouse. Two weeks after engrafting individual bioengineered teeth (or cellular primordia) into the exposed cavities, the transplants reportedly reconstituted into a correct tooth structure with enamel, dentin, root, pulp, and blood vessels.

The authors claim that their study “provides the first evidence of a successful reconstitution of an entire organ via the transplantation of bioengineered material.”¹ The study supports previous research in this area, including a 2004 study ⁶ that suggested the viability of bioengineering methods for generating tooth tissues in an animal model.

The new study adds to an evolving body of research on tissue bioengineering applications and mechanisms for regenerating dental structures in an animal model. Researchers around the world are exploring biologic mechanisms and stem cell techniques to develop dental regenerative therapies for the future. According to one recent study from the journal PLOS One ,⁷ the transplantation of human stem cells (from root apical papilla) into swine generated a root-periodontal complex that could support a porcelain crown.

Tooth organogenesis is a complex developmental process of epithelial and mesenchymal interactions. While emerging research suggests tremendous potential for tissue engineering applications in restorative dental care, the field is still in a preliminary stage, and the development of fully functional (and appropriately sized) tooth structures in animal and human models requires extensive scientific and clinical research. The ADA will continue to monitor the scientific literature on tissue bioengineering applications and provide information to the dental community as it becomes available.

1 Nakao K, Morita R, Saji Y, Ishida K, Tomita Y, Ogawa M, Saitoh M, Tomooka, Y, Tsuji T. The development of a bioengineered organ germ method. Nature Methods, Nature Publishing Group, February 18, 2007 (online). Available at: “http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth1012.html “. Accessed Feb. 23, 2007.

2 Japanese researchers grow teeth from single cells. Reuters, February 20, 2007. Available at: “http://today.reuters.com/news/articlenews.aspx? type=scienceNews&storyid=2007-02-20T105406Z_01_N18346540_RTRUKOC_0_ US-TEETH-MICE.xml ”. Accessed Feb. 23, 2007.

3 Reinberg S. Scientists grow mouse teeth from single cells. HealthDay, February 19, 2007. Available at: “http://www.healthday.com/Article.asp?AID=601946 ”. Accessed Feb. 23, 2007.

4 No more gaps for home-grown teeth. New Scientist, February 24, 2007, page 18. Available at: “http://www.newscientist.com/article.ns?id= mg19325925.100&print=true “. Accessed Feb. 23, 2007.

5 Chu J . Regrowing teeth. Technology Review, Cambridge, MA, February 22, 2007. Available at: “ http://www.technologyreview.com/Biotech/18216/ ”. Accessed Feb. 23, 2007.

6 Duailibi MT, Duailibi SE, Young CS, Bartlett JD, Vacanti JP, Yelick PC. Bioengineered teeth from cultured rat tooth bud cells. J Dent Res. 2004 Jul;83(7):523-8. Available at: “http://jdr.iadrjournals.org/cgi/content/full/83/7/523?ijkey=ce024890e02d5f1c355dcc17df7
c8d93de08120d ”. Accessed Feb. 23, 2007.

7 Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, Liu H, Gronthos S, Wang CY, Shi S, Wang S. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS ONE 1(1): e79. Available at: “http://www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.
pone.0000079 “. Accessed Feb. 23, 2007.

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Additional Resources

Journal of the American Dental Association

• The Impact of Tissue Engineering on Dentistry (March 2000)

• UConn Dental School Receives $12 Million to Study Stem Cells (Feb. 15, 2007)

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Science in the News is a service by the American Dental Association (ADA) to present current information about science topics in the news. The ADA is a professional association of dentists committed to the public's oral health, ethics, science and professional advancement; leading a unified profession through initiatives in advocacy, education, research and the development of standards. As a science-based organization, the ADA's evaluation of the scientific evidence may change as more information becomes available. Your thoughts would be greatly appreciated.

Document Posted February 2007

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