If We Could Continue to Generate Enamel We Would Never Have Cavities

One way to put dentists out of the drilling and filling business is to find a way to re-establish and stimulate something our bodies do when our teeth first form. Stem cell researchers at the University of Washington in Seattle may have figured out a potential treatment to repair damaged teeth and regenerate those we lose.

Hai Zhang, a professor of restorative dentistry at the University, along with several colleagues has found a way to generate ameloblasts. What are they? Ameloblasts are one of two cells that exist in human embryos responsible for the formation of our teeth. The other cells are called odontoblasts—the former secrete enamel, the latter dentin.

The process of tooth development is called odontogenesis. The two cells mentioned above are critical to tooth formation. Enamel keeps our teeth surfaces hard and strong throughout our lifetimes. Mineralization of teeth begins early in embryonic development. Dentin precedes enamel production, both critical to giving us a healthy set of choppers.

But life has its travails. What we eat and chew causes the enamel surfaces of our teeth to wear thin, crack and decay. And because it is embryonic cells that form the enamel and then die out once our teeth have been produced, we have no biological means to repair them.

Researchers decided to take on the task of trying to create these lost before-birth enamel-producing ameloblasts. To do they used single-cell combinatorial indexing RNA sequencing or sci-RNA-seq. This technique reveals which of the genes in a cell are active in sequence during development.

The RNA molecule is the letter carrier of the cell while genes are the letter writers. Hence the term messenger RNA or mRNA (a term for which many of us have become more familiar from mRNA COVID vaccines), the molecule that carries the instructions to assemble proteins which serve as the letter reader and construction crew in our analogy. Changes om levels of mRNA differ during stages of embryonic cell development which determines which of our genes are sequentially activated.

What the University of Washington researchers were able to do is track each gene activation stage and create a roadmap to develop ameloblasts from undifferentiated stem cells using a software tool called Monocle. The software was able to predict the biochemistry sequence to test on stem cells. They exposed the cells using computer-designed proteins and chemicals. The latter activated different genes in sequence to create the final roadmap. While doing the work on ameloblasts they uncovered another cell type, subodontoblasts which may precede the development of odontoblasts.

The end result was the stem cells were induced to create multicellular mini-organs called organoids which resembled the structures seen in developing human teeth. Now the team is hoping to improve the process to make enamel as durable as that found in a healthy mouth and develop methods for applying the technique to fill cavities and do other enamel restoration. Imagine a future where we have stem cells activated to fill cavities, do other enamel repair, and even replace lost teeth.

The results of the current project were published last week in the science journal, Developmental Cell.