Grow your teeth

The growing third : Offspring in the jaw

Rodents keep growing their incisors. Shark jaws continuously push new rows of teeth forward. And the molars of elephants are renewed up to seven times. But in humans nothing grows after the second teeth - except for the dentist's bills for bridges, implants or the dentition. Only in rare cases does a late, third pearly whale actually sprout from somewhere. These mostly tiny teeth are not enough for powerful biting, but they show that stem cells are dormant in the jaw for the next generation of teeth. Researchers now want to wake them from deep sleep.

Laser light awakens sleeping stem cells

David Mooney from Harvard University in Cambridge, USA, has now taken a step in this direction. With the help of low-energy laser light pulses, his team succeeded in stimulating human tooth stem cells to produce dentin, the bony tissue under the tooth enamel, which is also called dentin. According to the publication in the specialist magazine "Science Translational Medicine", the laser light in the dentin creates particularly reactive oxygen molecules. This activates a growth stimulator (TGF-beta-1), which awakens the dormant stem cells and stimulates them to form new dentin.
The advantage is that lasers are already being used in dentistry, says Mooney. Therefore, the method could perhaps be used in practices in just a few years. "It would be a big step forward if we could regenerate teeth instead of replacing them," says Mooney.
Around ten years ago, Paul Sharpe succeeded in growing living teeth in his laboratory at King’s College in London - but outside of the jaw in a Petri dish. Sharpe even set up a company, Odontis, to produce something called "Biotooth," even though he had only worked with mouse stem cells until now. Within two years, Odontis was to carry out the first human tests and transplant the first living teeth in twenty. But so far it has remained with the announcement.

Even Mooney should not be able to grow whole teeth with his laser pulse method, says his colleague Jeremy Mao from Columbia University. Mooney’s technique does solve a common problem in an impressive way: When caries treatments have to drill such a deep hole that the dentin or even the blood-supplied marrow is injured. Then the laser treatment could help that the dentin is reproduced, the tooth does not die and is preserved. “Whole teeth don't grow back in this way,” says Mao, who, unlike tissue culture expert Mooney, is a trained dentist. However, Mao's group is actually trying to grow whole teeth in the jaw. To do this, the researcher uses a porous framework made of a biodegradable polymer that is shaped like the patient's natural tooth and inserted into the patient's jaw. Unlike an implant, this scaffold is permeable to cells and is permeated with stimulating substances. These growth-promoting substances attract those cells from the patient's surrounding tissue that can reproduce a tooth.

Regenerative third parties: First tests on humans

Mao is already testing this procedure, which has already worked in rats, in the clinic - the first tests ever to enable third teeth to grow naturally in humans. The patients are those whose tooth is to be removed and a new one inserted, says Mao: “The dentist will send us CT images of the tooth that is to be removed, and we will then reconstruct an anatomically corresponding tooth framework and send it to the doctor Send implantation. ”In patients who have already lost a tooth, the tooth framework is reconstructed from the opposite tooth. But even Mao does not yet expect to be able to grow a complete tooth. The tooth enamel and probably also parts of the dentin have to be replaced by a crown.
According to Mao, the greatest hurdle in tooth regeneration is to find the right cells in the body with which all the components of a tooth can be reproduced. "We also have to learn how to direct these cells so that they form a tooth with the correct anatomical structures."
So that a tooth and no other organ actually grows, not only chemical molecules, but also very simple mechanics are necessary. For example, the agglomeration of cells in a very small space is important in order to begin tooth development. "This mechanical stimulation is more important for tooth regeneration than growth factors," says Don Ingber from the Wyss Institute for Biologically Inspired Engineering at Harvard University in Cambridge.
His research team has developed a gel that mimics the compression of cells. To do this, the tooth stem cells are first distributed in the gel. Once it is then transplanted into the body and exposed to normal body temperature, it will shrink. This brings the cells into close proximity - and stimulates the formation of teeth: "They start to form tooth-like bone material," says Ingber.

In order to regenerate a complete tooth, the mechanically activated cells have to be combined with other tooth-forming cells. Ingber implanted these so-called epithelial cells, from which skin and other surface organs are formed, together with mesenchymal cells in mice, where they stimulated the growth of a complete tooth with dentin, enamel and roots. Similar to Mao, Ingber's goal is to insert the gel and the necessary cells into the patient's jaw in order to grow a new tooth. “Interesting,” comments Mao, but so far Ingber has only used tooth stem cells from (mouse) embryos. "One of the hurdles before clinical tests is likely to be to find a source of stem cells in adults."

No unnecessary risk for new teeth

It is also still unclear whether artificial breeding of teeth does not pose a risk. If stem cells, which are supposed to no longer divide or even form teeth, are artificially stimulated, they could also grow into undesirable tissue types - in the worst case even grow cancerous. Mao believes that cells in your own body are under the control of growth factors. Using them is less risky than transplanting foreign cells from the laboratory.
It is questionable whether it makes sense to take any risk at all. After all, it's all about a beautiful smile, not life. "The metal implants used today are very successful - and can even withstand cola and other sweets," says Mao. But they are not ideal because they can also lead to inflammation and bone loss. In addition, artificial teeth do not grow and change together with the surrounding jawbone, as natural teeth do.
While researchers like Mao have so far only been able to grow teeth with the help of artificial scaffolding, in the future the human abilities dormant in the jaws will probably be reactivated to allow third teeth to sprout - whether by laser or syringe. “I really believe that it will be possible,” says Mao. When will that be? "You can't predict when a major scientific breakthrough will happen."

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