Mouse Tooth Created from Mouse Stem Cells

Proceedings of the National Academy of Sciences, August 3, 2009

Scientists at the Research Institute of Science and Technology at the Tokyo University of Science have announced the successful creation of a "tooth germ" from which an entire mouse tooth has been grown in vivo. The accomplishment is believed to have far-reaching implications and applications to a number of medical specializations that include the replacement of entire organs.

In an article entitled, "Fully functional bioengineered tooth replacement as an organ replacement therapy", the scientists report that, "This study represents a substantial advance and emphasizes the potential for bioengineered organ replacement in future regenerative therapies."

Led by Dr. Takashi Tsuji and using a method which they had developed two years ago, the researchers used mouse embryonic stem cells to create a "bioengineered tooth germ" - a tiny "package" of cells, approximately 500-micrometers in length, containing all the genetic instructions for the formation of a tooth - which the scientists then implanted inside a mouse's tooth socket from which a natural tooth had been removed. Approximately 5 weeks later, a new tooth erupted through the gum, and by 7 weeks the tooth was fully developed, complete with nerve fibers that were responsive to pain tests. The new tooth was found to exhibit all the properties of a natural tooth, with the one exception that it also appears to glow green when viewed under an ultraviolet light, since the scientists employed the common laboratory technique of tagging the genes with a green fluorescent protein in order to facilitate tracking of the genes. The process was then repeated in additional mice with identical results.

In 2007, using a similar proceedure the same team of researchers had been able to grow new teeth inside the bellies of mice, from which the teeth were then transferred to the jaws of mice. This new report, however, represents the first documented example of a bioengineered tooth that is fully functional because it has been completely grown in its natural habitat. In fact, the mice in whom the teeth were grown naturally responded to the presence of the new teeth by using them for the chewing of food.

As Dr. Kazuhisa Nakao, one of the authors of the study, explains, "Every bioengineered tooth erupted through the gum and had every tooth component such as dentine, enamel, pulp, blood vessels, nerve fibres, crown and root." According to Dr. Yasuhiro Ikeda of the Mayo Clinic in Rochester, Minnesota, such an accomplishment is "expected to evolve into a wide variety of organ-regenerative technologies for the liver, kidneys and other organs."

As the authors noted in their publication, "The bioengineered tooth, which was erupted and occluded, had the correct tooth structure, hardness of mineralized tissues for mastication, and response to noxious stimulations such as mechanical stress and pain in cooperation with other oral and maxillofacial tissues." As they further concluded, "The ultimate goal of regenerative therapy is to develop fully functioning bioengineered organs which work in cooperation with surrounding tissues to replace organs that were lost or damaged as a result of disease, injury, or aging. Here, we report a successful fully functioning tooth replacement in an adult mouse achieved through the transplantation of bioengineered tooth germ into the alveolar bone in the lost tooth region. We propose this technology as a model for future organ replacement therapies."