Test-tube teeth

POSTED 19 FEB 2004
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Why Files

More spare parts.

Repairing the spinal cord.

Sharks regenerate their own teeth. Someday, people may be able to do the same. Photo:NOAA.

chattering teeth say: If you can start the process off, nature will take its course and an organ – in this case, a tooth – will develop as it would in the embryo

Two cell types in the early embryo create a tooth. Epithelial cells become the enamel -- the hardest known biological substance -- and mesenchymal cells become the soft stuff inside. Diagram: NIH.

People have four basic kinds of teeth. Understanding the genetic signals that build them is key in tissue engineering. Illustration: National Library of Medicine.

A special talent lies behind a shark's fearsome grin. When a tooth -- among the rows and rows -- is lost, a fully-formed spare pokes through in a matter of days.

Shark displays rows of teeth.Must be nice.

Humans get a measly two sets. By age 50, the average person has lost 12 teeth, and by 70, half of us are toothless altogether, according to the National Institutes of Health.

Lucky for those of us who'd rather hang onto our molars, scientists are nursing human teeth in the laboratory with new success. Someday, this may mean the end of crowns and dentures for taffy addicts everywhere. It could also mean an end to the boundless suffering -- personal, social and economic -- caused by tooth loss worldwide.

In the days of imperial Rome, people hammered iron pegs in to replace missing teeth, and current technology is only slightly less grisly. Today's dental implants are made of materials like porcelain and titanium, but a metal screw must still be drilled into the gum. And implants don't always work, sometimes causing years of pain or discomfort. Teething doesn't sound so bad in comparison.

From the embryo to the lab
As an audience of scientists and reporters heard at the recent meeting of the American Association for the Advancement of Science, researchers are closer than ever to the test-tube tooth. Specifically, they are harnessing do-it-all stem cells to re-create the tooth buds that form in the early embryo. The idea is to implant these "primordial teeth" into human jaws and let the cells take it from there. Using a patient's own stem cells bypasses the rejection problems that so often happen in ordinary transplants.

"If you can start the process off, nature will take its course and an organ -- in this case, a tooth -- will develop as it would in the embryo," says Paul Sharpe of the Dental Institute at King's College in London. But like all approaches to tissue engineering, it's a complicated process.

One hurdle has just been cleared, says Sharpe. As he reported at the AAAS meeting, his team has successfully implanted a growing tooth from a mouse embryo into the mouth of an adult mouse and watched it grow.

Hold that thought
At this point, our interest was piqued. But we wonder: Why all this fuss for teeth? Our celebrity organs -- hearts, livers, lungs -- are waiting to make headlines when scientists grow them inside human bodies from stem cells.

And that hasn't happened yet. Teeth, Sharpe explains, make an appealing target for many reasons. If an engineered tooth grows in crooked or too small, a dentist can simply yank it out and start again. That wouldn't be so easy with vital organs. And getting access to the surgery site requires but a simple request: "open wide." No scalpel necessary.

Diagram of a tooth.

What's more, teeth have simple beginnings. They form from just two cell types in the embryo, epithelial cells and mesenchymal cells. The epithelium becomes enamel on the outside, and the mesenchyme forms the connective tissue and blood vessels inside.

The rudiments of the process are understood. Still, tooth development involves an elaborate network of thousands of genes. It isn't necessary to understand what all the genes are doing to get the ball rolling, Sharpe says. Rather, by watching when a few key genes are turned on and off, the researchers have learned which are most important in the control of size and shape. Some genes only work in the upper jaw, others only where molars grow. In one experiment, Sharpe's team took early tooth buds from growing embryos and switched on a gene known to be active in growing molars. They implanted the buds in the front of the jaws of mice, where incisors would normally grow. The rodents emerged with molars in front and back.

"By turning this gene on artificially, you can transform the way a tooth develops," Sharpe says.

The tooth speaks for itself
To see whether they could use stem cells to pull off a similar feat, Sharpe's team took tooth buds forming in a mouse embryo and replaced the mesenchyme with stem cells taken from an adult mouse. Stem cells can be prodded to convert into almost any tissue in the laboratory, when given the right signals.

The stem cells morphed into tooth tissue when they were implanted into a mouse kidney -- where the blood supply provides enough oxygen to get a complete tooth.

"For this we've concentrated on adult stem cells, because eventually for human patients, we don't want to be extracting embryonic stem cells," said Sharpe. (The advantage of using adult stem cells to regenerate human teeth is that the cells will come from the patient.)

Graphic shows set of human teeth.

Plenty of obstacles remain before the same can be done inside a human jaw. For one, Sharpe's is still working on creating tooth buds after replacing both the mesenchyme and the epithelium with stem cells. For another, the embryo and the mouth present very different environments. The mouth's connective tissue and bone could interfere with tooth development.

But Sharpe remains hopeful. After all, complete human teeth commonly grow inside ovarian cysts -- a tissue that bears little resemblance to the embryonic nursery. "This is an example were the embryonic process has proceeded normally in an adult environment, albeit a pathological one," Sharpe says.

"We have a long way to go. But by understanding...the important key genes, we can stimulate stem cells to form a tooth, as opposed to forming any other organ," he says. And that gives us all something to chew on.

-- Sarah Goforthlittle chattering teeth

Bibliography
"Tissue Engineering of Complex Tooth Structures on Biodegradable Polymer Scaffolds," C.S. Young et al., The Journal of Dental Research 81 (10):695-700, 2002.

"Development of teeth in chick embryos after mouse neural crest transplantations," Thimios A. Mitsiadis et al., Proceedings of the National Academy of Sciences, 100 (11): 6541-6545, 2003.

 

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