A Bioengineered Tooth Erupts Into Being

A new study describes the transplantation of a bioengineered tooth germ into alveolar bone of a mouse and its development into a fully functioning tooth, and proposes this as a model for future organ replacement therapy.

Researchers at Tokyo University of Science (Chiba, Japan), Organ Technologies (Tokyo, Japan), Tohoku University (Miyagi, Japan) and Tokyo Medical and Dental University (Japan) reconstituted a bioengineered molar tooth germ--that had developed at the early bell stage of a natural tooth germ--which was then transplanted with the correct orientation into an alveolar bone extraction site in the upper first molar region of an 8-week-old adult mouse. The cusp tip of the bioengineered tooth was then exposed into the oral cavity, and the vertical dimension of the tooth crown continually increased until the bioengineered tooth finally reached the plane of occlusion with the opposing lower first molar, 49 days after transplantation. During the course of eruption and occlusion, the alveolar bone gradually healed in the areas around the bioengineered tooth and the regenerated tooth had sufficient periodontal space between itself and the alveolar bone. The bioengineered tooth also formed a correct structure comprising enamel, ameloblast, dentin, odontoblast, dental pulp, alveolar bone, and blood vessels.

The researchers also evaluated the perceptive potential of the neurons that developed in the bioengineered tooth against noxious stimulations such as orthodontic treatment and pulp stimulation. The expression of galanin (a neuropeptide involved in pain transmission) increased in response to persistent painful stimulation of the nerve terminals within the periodontal ligament (PDL) of the bioengineered tooth to the same extent as in a normal tooth. The PDL nerve fibers in the bioengineered tooth appeared to respond to nociceptive stimulation caused by experimental tooth movements. Using sophisticated techniques for tracking genes with a fluorescent protein, the researchers also showed that genes that are normally active in tooth development were active during the bioengineered replacement tooth's growth. The study was published in the August 3, 2009, edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS)

"This study provides evidence of a successful replacement of an entire and fully functioning organ in an adult body through the transplantation of bioengineered organ germ, reconstituted by single cell manipulation in vitro,” concluded lead author Etsuko Ikeda, D.D.S., of Tokyo University of Science, and colleagues. "Further studies on the identification of available adult tissue stem cells for the reconstitution of a bioengineered tooth germ and the regulation of stem cell differentiation into odontogenic cell lineage will help to achieve the realization of tooth regenerative therapy for missing teeth.”

Related Links:
Tokyo University of Science
Organ Technologies
Tohoku University
Tokyo Medical and Dental University