Regrowing teeth: sharks can do it, crocodiles can do it, rodents can do it and humans - theoretically - too. Scientists at the Berlin Technical University (TU) are working on implementing this idea with dental pulp cells.
"Although there are occasional reports that people also grow back teeth or entire dental sets for the third time, why this happens in some people and not in others is still largely unknown," says Dr. Roland Lauster, Professor of Medical Biotechnology at the TU Berlin, describing the research project. "Basically, science assumes that the human jaw also has lifelong access to the information that is necessary for the growth of new teeth," said Dr. Jennifer Rosowski, scientific assistant for Dr. Lauster, who has dedicated her doctoral thesis to the topic of renewable teeth. The key question for them is what triggers this process.
Hair, teeth or even nails naturally develop as a result of mesenchymal condensation. In the case of tooth growth, certain precursor cells accumulate in the jaw below the outer skin layer. These cells condense and form a kind of tooth germ. As a result of this condensation, they begin to interact with the surrounding cell layers in the jaw via specific messenger substances. "Within the tooth bud formed in this way, different cell types are differentiated: the enamel organ, the dental papilla, and the dental ridge. These tissues gradually differentiate into a complete tooth," describes Dr. Rosowski. The information as to which tooth should be formed - incisor or molar - comes from the surrounding jaw tissue.
In their approach, the researchers from the TU Berlin extract dental pulp cells from the interior of an extracted tooth, which they cultivate in such a way that an active tooth germ is formed. If this tooth germ is implanted in a patient, the idea is that it begins to communicate with the surrounding tissue and thus triggers the cascade of messenger substances that initiate tooth formation.
Competing working groups have already provided conceptual proof in the animal model: they were able to show that a tooth germ implanted in the jaw actually grows back into a complete tooth.
However, Roland Lauster and his team see their own method as a decisive competitive advantage: "All competing research groups use embryonic stem cells to produce tooth germs. "This actually excludes the real application of the method, as the use of stem cells is highly controversial ethically in most countries and is not permitted by law," explains Jennifer Rosowski. "By contrast, we would only use cell material from the patient's own teeth. In this way, we avoid all ethical and legal concerns and have the decisive advantage that, in the case of a real application, it is the patient's own body tissue: The new tooth would therefore not cause a rejection reaction."
The teeth required for research were provided by the oral surgery department of the Charité University Hospital in Berlin in the form of wisdom teeth that had been surgically removed. The Berlin scientists have developed a special cultivation method in order to cause the adult cells contained in the teeth to de-differentiate again into a kind of embryonic state and then to aggregate into a tooth germ.
For this purpose, the dental pulp cells are separated, cleaned and then cultivated in microtiter plates, the surface of which is coated with a hydrogel. The hydrogel prevents the cells from adhering to the walls of the titer plates. They float freely in the medium but are actually programmed in such a way that they strive for a three-dimensional structure. As a result, they condense independently, without external pressure, into a kind of cell ball. This process takes 24 hours and the resulting cell ball is about 200 to 500 micrometers in size.
"We were the only group worldwide to be able to show that this independent mesenchymal condensation into a cell ball triggers the expression of different genes and initiates the production of specific messenger substances. These messengers are required in order to interact with the surrounding jaw tissue," said Jennifer Rosowski while explaining the method, which has since been patented worldwide.
In order to prove this inductance, the scientists co-cultivated the tooth germs with cells from the gums. During embryonic tooth development, these two cell types interact and trigger tooth formation. Now that all in vitro experiments have been successfully completed, the tooth germs are ready for the first preclinical tests.