Takashi Tsuji/Tokyo University of Science

Good as new. A bioengineered tooth germ placed in the jaw of a mouse (top) buds through the gum at 36 days (center) and fully grows in after 49 days (bottom).

Researchers Grow New Teeth in Mice

If you've lost a tooth to decay or injury, you may not have to rely on that dental bridge or implant forever. Japanese scientists have found a way to bioengineer new adult teeth. So far, the method only works in mice, but experts say it may one day take hold in humans.

The Japanese group, led by cell biologist Takashi Tsuji of Tokyo University of Science in Noda, Chiba Prefecture, focused on tooth germs, the embryonic tissues that develop into teeth. After obtaining such germs from mouse embryos, they separated out two types of cells--epithelial cells and mesenchymal cells--and then recombined them into a new bioengineered tooth germ. (Tsuji says that he and colleagues wanted to demonstrate that, for future human clinical applications, they could likely start with epithelial and mesenchymal cells derived from a patient's own stem cells.) The team then grew the bioengineered germs in a special culture for 5 to 7 days and transplanted them into the upper jaws of adult mice in the place of an extracted molar. New teeth poked through the gums after about 36 days and reached the proper size and alignment with opposing teeth for proper chewing after 49 days, the group reports online today in the Proceedings of the National Academy of Sciences.

All indications are that the teeth function just like the real thing. They have the roots, inner pulp, and outer enamel of normal teeth and are just as hard, the team reports. Moreover, unlike dental implants, the regenerated teeth develop the periodontal ligaments that tie normal teeth to the supporting bone and the nerve fibers that give sensitivity to chewing pressure and other stresses. "We clearly demonstrated that the bioengineered organ germ could develop into a fully functioning organ," Tsuji says.

"This is a significant advancement," says Irma Thesleff, a developmental biologist at the University of Helsinki. She notes that the group built on previous work, "but it is the first time that it is demonstrated that starting from [just two cell types] an extracted tooth can be replaced" with a functional grown-in-place tooth. Masaki Shimono, a dental scientist at Tokyo Dental College in Chiba, says the formation of normal roots is apparently a first, "though many studies succeeded in forming tooth crowns." He says further challenges include demonstrating the formation of different kinds of teeth and the proper location of cusps. Tsuji admits that although the bioengineered teeth are functional, the crown widths, cusp positions, and tooth patterning were not quite normal. But he expects his group to gain control over such details with further research.

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