The regeneration of fully functioning tooth by cell manipulation

Technology for reconstituting an entire organ from single cells is expected to be applied for replacement of organs lost or damaged due to disease, injury, or aging in regenerative therapy. In this study, we demonstrated that a bioengineered primordial organ from epithelial and mesenchymal cells of murine tooth germ successfully achieved eruption and developed into a tooth with proper functions in adult oral environment. The bioengineered primordia were transplanted in upper alveolar bone, where upper first molars had been extracted and healing of extraction wounds had been completed. At 30 days after transplantation, exposure of cusp tip into the oral cavity occurred, indicating an eruption of the bioengineered tooth. At 50 days and thereafter, this bioengineered tooth reached the occlusal plane and achieved opposing tooth occlusion. Micro-CT Images showed that the bioengineered tooth had the unit of a tooth, periodontal ligament, and alveolar bone similar to the normal tooth. These findings indicated that the bioengineered tooth could contribute to mastication, an important oral function. The tooth bioengineered by the cell manipulation techniques may have cooperated with the oral and maxillofacial regions and fulfilled oral functions of a mature organ, including mastication. Our study results may have advanced the understanding of the possible application of bioengineered organs in future regenerative therapies.