Paul Sharpe, a dental researcher at King’s College, London, is not too worried about eating sweets. As any dentist would be happy to remind him, such sugary treats will rot his teeth. But Dr. Sharpe believes that his researches should one day enable him––and everyone else––to grow a completely new set of gnashers.
Although human babies are born without visible teeth, they have “proto-teeth” hidden in their gums. These proto-teeth, known as primordial, derive from an interaction between two basic cell types, called epithelial and mesenchymal cells. By culturing these cells, and putting them together as they would come together naturally, Dr. Sharpe has managed to form an artificial primordium.
To do so, he starts with human neural stem cells (these are undifferentiated cells similar to those found in embryos, and which are capable of developing into a variety of cell types). He aggregates his stem cells into small pieces of tissue, then overlays a piece of oral epithelium on them. The cells of oral epithelium already know they are supposed to become part of a tooth, and they “instruct” the stem cells to turn into oral mesenchymal cells. When the resulting primordium is transplanted into a mouse kidney (a good environment for this sort of thing, since it is well supplied with blood and oxygen) it turns into a tooth.
Dr. Sharpe has dubbed this area of research “regenerative dentistry”. His hope is that it will become possible to implant the primordium into a patient’s gum, in the place of a removed or lost tooth. After implantation, it would grow, form roots that would attach themselves to the jaw, and eventually erupt into the mouth after only a few weeks.
For the process to work reliably, however, it will be necessary to persuade the primordium to develop into a full-fledged tooth. This would be done by activating appropriate genes. The trick remaining is to identify exactly which ones. Though thousands of genes are involved in the development of an organ such as a tooth, these genes are switched on in a cascade, with the activity of one triggering the activation of the next. So it is only necessary to identify, and mesenchymal ick-start, the first genes in the cascade, which are likely to be few in number. One such gene that has already been identified is called Barxi. This gene is expressed only in cells in primordial that are destined to become molars, so it is probably a gene that controls the shape of a tooth.
With populations in rich countries getting long in the tooth, as it were, it seems likely there will be a huge demand for regenerative dentistry. To exploit that demand, Dr. Sharpe has started a company called Odontis. If it succeeds in commercializing his stem-cell technology, its shareholders will, indeed, have plenty to smile about.
© 2004 The Economist Newspaper Ltd. All rights reserved. Reprinted with permission. Further reproduction prohibited. www.theeconomist.com
Dentigenix Inc., bringing advances in regeneration biology to dentistry
Dentigenix Inc., the biotechnology group of Ivoclar Vivadent, is working to bring recent advances in regeneration biology and tissue engineering to the practice of dentistry. They are pursuing dental tissue regeneration therapies including a cooperative effort with the Forsyth Institute to re-grow whole adult teeth using intellectual property licensed from Harvard Medical School, Massachusetts General Hospital, the NIH and others.
Working in conjunction with researchers in the U.S. and Europe over the next several years, Dentigenix will be introducing a series of therapies designed to repair and/or replace lost dental tissue with completely natural tooth structure. The technical know-how to accomplish this comes from a variety of scientific disciplines and involves the use of growth factors, cellular processes and bioengineering as well as knowledge of developmental biology and genetics. Erick Rabins, COO of Dentigenix, comments, “Assembling the right team, scientific advisors and intellectual property is half the battle; commitment, tenacity and just plain luck are essential ingredients as well.”
For more information please visit the Dentigenix Web site at www.dentigenix.com.