Unique cellular and molecular mechanisms behind tooth renewal in American alligators may help science learn how to stimulate tooth regeneration in people, according to a new study.

We regenerate teeth now. We grow baby teeth and then we replace those with adult teeth.  Yet most vertebrates can replace teeth throughout their lives and we cannot, despite the lingering presence of dental lamina, a band of epithelial tissue crucial to tooth development. Because alligators have well-organized teeth with similar form and structure as mammalian teeth and are capable of lifelong tooth renewal, the authors reasoned that they might serve as models for mammalian tooth replacement. 

 Using microscopic imaging techniques, the researchers found that each alligator tooth is a complex unit of three components - a functional tooth, a replacement tooth, and the dental lamina—in different developmental stages. The tooth units are structured to enable a smooth transition from dislodgement of the functional, mature tooth to replacement with the new tooth.

Identifying three developmental phases for each tooth unit, the researchers conclude that the alligator dental laminae contain what appear to be stem cells from which new replacement teeth develop.

"Ultimately, we want to identify stem cells that can be used as a resource to stimulate tooth renewal in adult humans who have lost teeth. But, to do that, we must first understand how they renew in other animals and why they stop in people," said University of Southern California pathology Professor Cheng-Ming Chuong, M.D., Ph.D.
and co-author of the paper in PNAS.

"Alligator teeth are implanted in sockets of the dental bone, like human teeth," said Ping Wu, Ph.D., assistant professor of pathology at the University of Southern California Keck School of Medicine and first author of the study. "They have 80 teeth, each of which can be replaced up to 50 times over their lifetime, making them the ideal model for comparison to human teeth."

The authors also report novel cellular mechanisms by which the tooth unit develops in the embryo and molecular signaling that speeds growth of replacement teeth when functional teeth are lost prematurely.  

"Stem cells divide more slowly than other cells," said co-author Randall B. Widelitz, Ph.D., associate professor of pathology at the Keck School of Medicine. "The cells in the alligator's dental lamina behaved like we would expect stem cells to behave. In the future, we hope to isolate those cells from the dental lamina to see whether we can use them to regenerate teeth in the lab."

The researchers also intend to learn what molecular networks are involved in repetitive renewal and hope to apply the principles to regenerative medicine in the future.