According to the U.S. Department of Health and Human Services, the average American will lose about eight teeth by the time he or she turns 50. Common replacements include dentures, which have been known to erode the underlying bone over time, and dental implants, which are prone to falling out after several years’ use. Thus, the ability to regrow a natural tooth, with the accompanying bone, root, and nerves, could provide a significantly healthier alternative for many.
Recently, a Japanese team from the Tokyo University of Science, led by associate professor Takashi Tsuji, reported in Nature Methods that it had successfully regrown a tooth from cells extracted from mouse embryos. The researchers were able to transplant the tooth into an adult mouse, and the tooth bud continued to grow to full size.
Teeth in mice, much like those in humans, form during embryonic development from two major cell types: epithelial and mesenchymal. Epithelial cells give rise to the outer enamel, while mesenchymal cells form a tooth’s inner connective tissue and blood vessels. Takashi’s team isolated both kinds of cells from multiple mouse embryos, then transferred them to a collagen gel culture, in which the cells interacted to form a tooth bud. Researchers then transplanted the bud into the liver of an adult mouse, where the increased blood supply aided further tooth formation. Finally, Takashi inserted the tooth into an empty cavity within the mouse’s mouth, in which it grew to full size.
Whether the technique will be practical for regrowing teeth is uncertain. Paul Sharpe, head of the Craniofacial Development Department at King’s College, in London, doubts that the technique will be useful for humans, particularly since the Tokyo team used embryonic cells, which are difficult to obtain in large numbers and may be rejected as a foreign substance when transplanted into a human adult.
A better approach, Sharpe suggests, may be to use adult stem cells, which can be obtained from a patient’s hair, skin, or other tissue; manipulated with the right molecular cues to form any kind of tissue; then transplanted back into the same person with less rejection problems.. Sharpe’s lab is looking for adult stem cells, including those found in bone marrow and dental gum, as possible candidates for regrowing teeth. So far, he and his colleagues have had success with bone-marrow stem cells, forming teeth and transplanting them into mouse cavities. However, Sharpe says that obtaining such cells from human bone marrow is a painful process. In the next three years, he hopes to identify more-accessible stem cells that may be able to form not only teeth, but also–and more important–roots.
“If you think about it, you are transplanting a tooth under the soft tissue, in the gums,” says Sharpe. “That tooth has to erupt and form roots so it’s connected. If you can’t form a root, there’s no point doing any of it.”
Indeed, a group of researchers from the University of Southern California (USC) recently regrew tooth roots in pigs using adult stem cells from wisdom teeth. The team, led by Songtao Shi, assistant professor of USC’s School of Dentistry, isolated stem cells from the extracted wisdom teeth of 18-to-20-year-old humans. From these cells, the researchers successfully recreated a tooth’s root and periodontal ligament, which, when transplanted into the oral cavity of a pig, could support a synthetic crown. Shi says it is a promising start, and his team hopes to begin human trials within the next few years. Eventually, he envisions being able to isolate stem cells from sources such as wisdom teeth, then store them for future use should the patient require dental attention down the line.
In the next few years, Shi, Sharpe, and others anticipate great strides in the area of tooth regeneration. As Sharpe sees it, the work being done in his field may help researchers in other areas of tissue engineering.
“I like to think that the fact that we are working on an organ where the surgery is easy to do and accessible will mean we can iron out some of the problems more easily in a patient,” says Sharpe. “If we do something in a patient and it doesn’t work, it’s very easy to correct: the patient just has to come in and open his mouth. If doing that with a liver or a heart, it’s not quite so easy. So we might prove certain principles of organ engineering.”
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