U.S.- Brazil Team Bioengineers Tooth Crowns In Second Mammal Species

The advance follows Forsyth’s widely-publicized regeneration of pig tooth crowns in 2002 and adds evidence that it may, one day, be possible to grow new human teeth from an individual’s own cells.

“We are very excited because mammalian systems tend to operate in similar ways,” said Pamela Yelick, PhD, Assistant Member of the Forsyth Staff and the principal investigator. “Having regenerated teeth of a second mammalian species allows us to hope for similar success with human teeth.”

In their newly reported work, the Forsyth team found that it was possible to maintain individual tooth-forming cells in culture for six days before implanting them— thus demonstrating that adult dental stem cells can give rise to tooth crowns containing dentin and enamel and indicating that it might be possible to expand enough such cells in culture to grow full-sized teeth.

The advances are reported in the July 2004 Journal of Dental Research, which also includes a British team’s article on the use of non-dental stem cells to grow tooth primorida in mice and an editorial describing “the immense potential” for regenerative and tissue-engineering applications to dentistry.

In the words of Dominick P. DePaola, DDS, PhD, The Forsyth Institute’s President and Chief Executive Officer, “This groundbreaking science heralds a revolution in dentistry, in which biological tools will increasingly replace mechanical ones. ”

Paulo Augusto de Lima Pontes, MD, PhD, coordinator of the UNIFESP Post-Graduation Department of Otorhinolaryngology and Head and Neck Surgery, said: “ The results shown by the Forsyth-MGH- UNIFESP team promise new therapeutic options in dental medicine.”

In bioengineering rat teeth, the scientists used techniques similar to those previously used at Forsyth to form pig teeth. In both sets of experiments, researchers “seeded” cells obtained from immature teeth of animals onto biodegradable polymer scaffolds. The scaffolds were then implanted in the abdomen of rat hosts. Within three-to-six months, depending on the particulars of the experiment, small, recognizable tooth crowns formed.

Previously, Forsyth researchers had grown small teeth from dissociated pig molar buds, but could not be certain that the new teeth had not emerged from "clumps" of incompletely dissociated tooth tissue. In the newly reported work, the scientists grew individual, dissociated tooth bud cells in culture before implanting them.

In both sets of experiments, the Forsyth scientists used “adult” dental stem cells, which give rise only to dental tissue. They did not use “embryonic” stem cells, which can be induced to form a variety of different tissue types.

According to Monica T. Duailibi, DDS, PhD, the paper’s first author, “Our results show that individual tooth progenitor cells can interact on scaffolding to form tooth crowns and that it might be possible to culture enough dental stem cells to grow full-sized teeth.” Dr. Duailibi conducted the work at Forsyth along with Silvio E. Duailibi, DDS, PhD, when both were doctoral candidates at UNIFESP. Both are currently post doctoral researchers in the UNIFESP Department of Otorhinolaryngology and Head and Neck Surgery.

The scientists’ goal is to develop methods for replacing lost or missing human teeth by growing new teeth, in an individual’s jaw, from an individual’s own cells.

They are currently working on the possibility of growing new teeth in a mammalian jaw, and are beginning to work with human tooth tissues. “Within a year, we expect to determine whether the methods we use to regrow animals’ teeth will be useful in regenerating human teeth,” Yelick said. “If the methods prove effective, it will be at least seven years before they can be tested clinically in humans.”

In the words of collaborator Joseph P. Vacanti, MD, "Dr. Yelick and the combined team have made enormous progress towards the development of an engineered living tooth. As more knowledge is gained into the biologic and genetic mechanisms of tooth development, rational approaches in building living teeth from stem cells are now progressing from imagination into reality". Dr. Vacanti is Chief of the Department of Pediatric Surgery; Surgeon-in-Chief, Hospital for Children; Director of Pediatric Transplantation, and Director of the Laboratory for Tissue Engineering and Organ Fabrication, all at Massachusetts General Hospital.

According to Bruce Donoff, DMD MD, Dean of the Harvard School of Dental Medicine, “Having helped fund this important research, we are proud to be collaborators in this future direction of dentistry. These advances are moving the field from technique-driven restoration to those based on biological solutions through regeneration. The possible impact on dental practice and oral health is far-reaching.”

In addition to Drs. Yelick, Duailibi, and Vacanti, team members included Conan S. Young, PhD and John D. Bartlett, PhD of the Department of Cytokine Biology at The Forsyth Institute.

The research was funded by the Harvard School of Dental Medicine and the Center for Integration of Medicine and Innovative Technology, with additional support from CAPES (Coordenação de Aperfeiçoamento de Pessoal de nível Superior); UNIFESP; and The Forsyth Institute.