Organoids Produce Tooth Enamel Proteins

Researchers at the University of Washington School of Medicine have developed a method to create stem cell-derived organoids that can produce tooth enamel proteins. The breakthrough could pave the way for lab grown enamel that can be used in dental repairs and may even allow for living fillings or completely new living teeth that can be implanted into a patient’s jaw. The researchers studied the genetic activity that occurs during tooth development, and then used this information to steer stem cells into becoming ameloblasts, which are the cell type responsible for enamel creation. Once present in organoids, the cells can produce three proteins that are crucial in enamel.

Repairing teeth is difficult. In the past, people would simply have them all pulled out and use false teeth instead. Thankfully, modern dentistry is somewhat more sophisticated, but still rarely involves actually regenerating damaged or diseased dental tissue, and usually means removing and replacing tissue with synthetic alternatives. While this is OK, it would be nice to be able to replace missing teeth with a living alternative or plug a hole in a tooth with real tooth enamel, rather than a synthetic polymer paste.    

Creating regenerative treatments for dental work is a noble goal, but is faced with a key challenge, at least in the case of tooth enamel. During tooth formation, enamel is created by cells called ameloblasts. However, these cells only stick around during tooth formation and die off thereafter. Therefore, teeth have no way to regenerate their own enamel and there is no endogenous population of such cells to target in adult patients. The researchers behind this latest study realized that if they wished to create tooth enamel naturally, then such cells would need to be created from near scratch. And that’s what they did.

The researchers used a tool called single-cell combinatorial indexing RNA sequencing (sci-RNA-seq) to study which genes are turned off and on at each point during tooth development, giving them a blueprint of ameloblast development. Then, they activated those same genes, in the correct sequence, to coax undifferentiated stem cells to develop into ameloblasts, which they grew as organoids. Strikingly, the organoids produced proteins that are crucial for enamel development, indicating a first step on the path to regenerative dental treatments.  

“Many of the organs we would like to be able to replace, like human pancreas, kidney, and brain, are large and complex. Regenerating them safely from stem cells will take time,” said Hannele Ruohola-Baker, a researcher involved in the study. “Teeth on the other hand are much smaller and less complex. They’re perhaps the low-hanging fruit. It may take a while before we can regenerate them, but we can now see the steps we need to get there. This may finally be the ‘Century of Living Fillings’ and human regenerative dentistry in general.”