Alligator Stem Cells and Tooth Replacement


Mammals usually have one set of baby teeth (also known as milk teeth) and after those are lost, we have one set of adult teeth and these are not replaced if they are lost. This condition is called “monophyodont.” Reptiles and sharks, however constantly replace their teeth. This condition is called “polyphyodont.” Alligators and crocodiles are among one group of reptiles that replace their teeth throughout their lives, and because the development of these creatures has been studied to some extent, it is known that the ability of these creatures to replace their teeth on a regular basis results from a resident stem cell population. Studying that stem cell population more closely might provide clues for tooth replacement in humans.

American Alligator
American Alligator

A research team led by scientists at the Keck School of Medicine professor of pathology Cheng-Ming Chuong at the University of Southern California. Dr. Chuong and his collaborators from around the world have identified unique cellular and molecular mechanisms behind tooth renewals in American alligators.

Chuong explained, “Humans naturally have only two sets of teeth – baby teeth and adult teeth. 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.”

Even though humans cannot replace their adult teeth, a tissue called the dental lamina remains, which is known to be crucial for tooth development.

Why are alligators potentially a good model system for tooth replacement in mammals? First author of this study, Ping Wu, explained it this way, “Alligator teeth are implanted in sockets of the dental bone, like human teeth. 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.”

Through the use of microscopic imaging techniques, Chuong and others found that each alligator tooth is a complex unit of three components: a functional tooth, a replacement tooth, and the dental lamina, all other which are at different developmental stages.

The tooth units are built to enable a smooth transition from dislodgement of the functional, mature tooth to replacement with a new tooth. Further imaging studies strongly suggested that the dental lamina contains a stem cell population from which new replacement teeth develop.

“Stem cells divide more slowly than other cells, said co-author Randall B. Widelitz, who serves as an associate professor of pathology at USC. Widelitz continued, “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.

The authors also noted that novel cellular mechanisms are used during the development of the tooth unit. Also, unique molecular signaling speeds growth of replacement teeth when functional teeth are lost.

See P. Wu PNAS 2013; DOI: 10.1073/pnas.12132110.

Stem Cells From Gum Tissue Help Replace Missing Teeth


Researchers from King’s College London, UK have developed a new method that replaced missing teeth with bioengineered material made from a patient’s own gum cells.

If a patient loses a tooth, the dentist or oral surgeon will typically replace it with an implant. The vast majority of dental implants used today are root-form endosseous implants. Such implants have a similar look to an actual tooth root and are placed within the bone of the jaw. The bone of the jaw fuses the surface of the implant with the surrounding bone (a process known as osseointegration). Because dental implants lack the periodontal ligament they will feel slightly different from natural teeth during chewing. Also, the friction from chewing and from other jaw movements can cause loss of bone around the implant.

??????????????

Research by members of Paul Sharpe‘s laboratory at King’s College London has brought us closer to the reality of bioengineered teeth to replace toss teeth. Bioengineered tooth research has focussed primarily on producing immature teeth that can grow into adult teeth. Typically, such tooth buds are grown in culture and then transplanted into the gums. The gum actually provides and adequate environment for embryonic tooth buds to develop and form adult teeth. Therefore, the prospect of forming bioteeth certainly seems viable. The only question is identifying the cells and materials that can combine to properly form a normal adult tooth.

TOOTH DEVELOPMENT

Sharpe noted, “What is required is the identification of adult sources of human epithelial and mesenchymal cells that can be obtained in sufficient numbers to make biotooth formation a viable alternative to dental implants.”

Sharpe and his colleagues surmised that gum tissue might provide the right cells for this project. Therefore, they isolated adult human gum tissue samples from patients at the Dental Institute at King’s College and grew it in culture in the laboratory. Next, Sharpe’s group combined this gum tissue with mouse embryonic tooth mesenchyme cells, which are stem cells that can induce tooth formation.  This gum-tooth combination created teeth with surrounding gum tissue that could be transplanted into the mouths of mice. The teeth had dentine, enamel and viable roots.

The epithelial cells from human gum were able to respond to tooth-inducing signals from the embryonic tooth mesenchymal cells in a manner that allowed them to contribute to the tooth crown and the roots, and formed all the available cell types necessary for normal tooth formation. Thus, it appears that gum biopsies can provide a realistic source for human biotooth production.

The next step in this research is the formidable challenge of finding a mesenchymal stem cell population that can induce tooth formation. Presently, only embryonic mesenchymal cells can do this, according to Sharpe, but it is possible that adult mesenchymal stem cells can be manipulated to become tooth-inducing cells.