As tissues go, teeth are relatively simple. They only consist of a few cell types, arranged in a rather straight-forward manner. Therefore, regenerating teeth, while more difficult than it seems, should represent a tractable problem for stem cell biologists and tissue engineers. While some progress has been made, tooth regeneration procedures will require more fine-tuning before they will be hailed as successful.
Tzong-Fu Kuo and others from the School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan have examined the feasibility of whole-tooth regeneration in minipigs. Kuo and his group used a tissue-engineered tooth germ-like construct.
To construct their tooth germ constructs, Kuo and his colleagues extracted dental pulp from upper incisors, canines, premolars, and molars from mature miniature pigs. They grew the dental pulp tissue in culture in order to expand the faster-growing dental pulp stem cells (DPSCs) that can outgrowth everything else from the pulp in culture. They differentiated the DPSCs into odontoblasts, which make the dentine of the tooth, and osteoblasts, which make bone. Kuo’s team also acquired gingival epithelial cells from the gums of the minipigs.
Next the gum epithelial cells, odontoblasts, and osteoblasts were implanted onto the surface (upper, and lower layers, respectively), of a bioactive scaffold. This scaffold had the odontoblasts inside, the osteoblasts outside, and the gum epithelial cells outside the osteoblasts. Then Kuo and his coworkers transplanted these seeded bioactive scaffolds into the tooth sockets of the lower jaw of a minipig whose lower first and second molar tooth germs were removed.
13.5 months after the scaffolds were implanted, seven of eight pigs had formed two new teeth that had crowns, roots, and pulp. When the newly-formed teeth were extracted and sectioned, they had enamel-like tissues, dentin, cementum, odontoblasts, and periodontal tissues.
A fascinating finding in this study was that all the pigs, without exception, had regenerated molar teeth regardless of the original tooth from which the DPSCs were isolated. As an important control, minipigs that had their tooth germs removed or received empty scaffolds did not develop teeth.
This study from Kuo’s laboratory showed that implantation of a tooth germ-like structure can produce a complete tooth can do so successfully and efficiently. This study also established that the location of the implant seemed to deeply influence the morphology of the regenerated tooth.