New research examines ameloblasts, holds promise for regenerative dentistry

August 31, 2023  14:08

Murine models have been instrumental in studying tooth development; however, significant differences in tooth shape, number of cusps, and the timing and sequence of molar development between mice and humans necessitate a deeper understanding of human tooth development to develop effective treatments for dental disorders. Seeking to advance research in enamel regeneration, a recent study has examined the regulatory mechanisms of ameloblasts and investigated how they develop and function. The insights gained have implications for both understanding conditions that affect the enamel and potentially developing regenerative approaches for dental health.

“This is a critical first step to our long-term goal to develop stem cell-based treatments to repair damaged teeth and regenerate those that are lost,” co-author Dr Hai Zhang, professor of restorative dentistry at the University of Washington (UW) School of Dentistry in Seattle, said in a press release.

Using a method of examining tooth development at the single-cell level applied to cells at different stages of human tooth development, the researchers were able to capture the patterns of gene activation at each stage. They then used a computer program to construct the likely trajectory of gene activities that occur as undifferentiated stem cells develop into fully differentiated ameloblasts and with the program induced the development of human stem cells into ameloblasts by exposing them to chemical signals that activated different genes according to this sequence.

“The computer program predicts how you get from here to there, the road map, the blueprint needed to build ameloblasts,” said senior author Dr Hannele Ruohola-Baker, an adjunct professor of oral health sciences at UW School of Dentistry and an associate director of the UW Medicine Institute for Stem Cell and Regenerative Medicine.

During the project, the scientists also identified another cell type, a subodontoblast, which they believe to be a progenitor of odontoblasts. They discovered that these cell types could be induced to form organoids, which then become organised into structures similar to those seen in developing human teeth and secrete three essential enamel proteins, namely ameloblastin, amelogenin and enamelin. Once a matrix is formed, a mineralisation process can begin.

The researchers now hope to make an enamel that is as durable as that of natural teeth and to develop ways to use it to restore damaged teeth. The ultimate goal is to create stem cell-derived teeth that could completely replace lost teeth.

“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,” Dr Ruohola-Baker noted. “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,” she added.

“This may finally be the ‘century of living fillings’ and human regenerative dentistry in general,” she concluded.

The study, titled “Single-cell census of human tooth development enables generation of human enamel”, was published online on 14 August 2023 in Developmental Cell.

 

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