Forsyth Researchers Regenerate Mammalian Teeth

"The ability to identify, isolate and propagate dental stem cells to use in biological replacement tooth therapy has the potential to revolutionize dentistry," said Dominick P. DePaola, DDS, PhD, president and chief executive officer of The Forsyth Institute, the independent research organization where the work was conducted.

Joseph P. Vacanti, MD, director of the Laboratory for Tissue Engineering and Organ Fabrication at Massachusetts General Hospital (MGH) and a co-author, called the work "important" in several respects: "It points the way for biologic repair in dental disease using the new tools of tissue engineering. It suggests the existence of stem cells, which could be important in many areas of dental repair. And, by combining the new science of stem cell biology with the engineering concepts and techniques of tissue engineering, it demonstrates that complex structures such as living teeth can be created."

As reported in the October 1, 2002 Journal of Dental Research, the Forsyth researchers seeded cells obtained from immature teeth of sixth-month old pigs onto biodegradable polymer scaffolds and placed them in rat hosts. Within 30 weeks, small, recognizable tooth crowns had formed.

These crowns contained dentin (a bone-like layer); odontoblasts (cells that secrete the proteins that form dentin), a well-defined pulp chamber; Hertwig’s root sheath epithelia, cementoblasts (cells that form a mineralized tissue that covers the roots of the tooth), and, significantly, a morphologically correct enamel organ.

The Forsyth results, demonstrated in some two dozen experiments, represent the first successful generation of mature tooth crowns containing both dentin and enamel. The results also suggest that it may be possible to grow teeth of a particular size and shape, according to Pamela C. Yelick, PhD, the principal investigator, an Assistant Member of the Staff at Forsyth.

Previous researchers had used alternative approaches to form partial tooth structures including dentin and pulp, but none had grown complete structures that included enamel.

The Forsyth team is the first to report using dissociated tooth tissues (tooth buds enzymatically digested into single cells) combined with polymer scaffolding (a technique used elsewhere to regrow other bodily human tissues) to regenerate teeth.

Also of great importance is the discovery that dental stem cells appear to exist in porcine third molar tissues. "Finding putative epithelial and mesenchymal dental stem cell populations in mammals suggests that similar cells might exist in human beings," Yelick said.

Yelick predicts that within five years, "we will know whether dental stem cells can be manipulated to bioengineer teeth. To generate a human tooth might take an additional five to ten years."

The Forsyth research was supported, in part, by the Center for Integration of Medicine and Innovative Technology, a nonprofit consortium of academic and research institutions, and by the Harvard School of Dental Medicine Center for Craniofacial Tissue Engineering. "It is very gratifying to see the vision to create a biologic tooth come into view," said HSDM Dean Bruce Donoff, DMD, MD. "The potential of this advance is enormous and could have a far-reaching impact on patient care."

The research, described in "Tissue Engineering of Complex Tooth Structures on Biodegradable Polymer Scaffolds," was conducted at The Forsyth Institute, an independent, nonprofit research organization focusing on oral, craniofacial and other biomedical sciences.

Principal Investigator Pamela C. Yelick, PhD, Assistant Member of Staff in the Department of Cytokine Biology at Forsyth, led the scientific team. She is also an instructor at the Harvard School of Dental Medicine (HSDM). The research team included: lead author Conan S. Young, PhD, research associate, and John D. Bartlett, PhD, associate member of the staff, both of The Forsyth Institute; Shinichi Terada, MD, and Joseph P. Vacanti, MD, both of the Departments of Surgery at MGH and HMS; and Masaki Honda, DMD, PhD, of the Department of Oral and Maxillofacial Surgery, Nagoya University School of Medicine in Nagoya, Japan.