Dental enamel created from stem-cells
Advance seen as step towards repair and regeneration of teeth
Organoids have been created from stem cells to secrete the proteins that form dental enamel. Organoids are simple tissue-engineered cell-based in vitro models that recapitulate many aspects of the complex structure and function of the corresponding in vivo tissue.
“This is a critical first step in our long-term goal to develop stem cell-based treatments to repair damaged teeth and regenerate those that are lost,” said Hai Zhang, professor of restorative dentistry at the Washington University School of Dentistry and one of the co–authors of the paper describing the research.
The findings were published in the journal Developmental Cell1.
This may finally be the ‘Century of Living Fillings’
During tooth formation enamel is made by specialised cells called ameloblasts and when formation is complete these cells die off; consequently, the body has no way to repair or regenerate damaged enamel.
To create ameloblasts in the laboratory, the researchers first had to understand the genetic programme that drives fetal stem cells to develop into these enamel-producing cells. They used a technique called single-cell combinatorial indexing RNA sequencing (sci-RNA-seq), which reveals which genes are active at different stages of a cell’s development.
By performing sci-RNA-seq on cells at different stages of human tooth development, the researchers were able to obtain a series of snapshots of gene activation at each stage. They then used a computer programme to construct the likely trajectory of gene activities that occur as undifferentiated stem cells develop into fully differentiated ameloblast.
“The computer program predicts how you get from here to there, the roadmap, the blueprint needed to build ameloblasts,” said Hannele Ruohola-Baker, Professor of Biochemistry, who headed the project. With this trajectory mapped out, the researchers were able to coax undifferentiated human stem cells into becoming ameloblasts by exposing the stem cells to chemical signals that were known to activate different genes in a sequence that mimicked the path revealed by the sci-RNA-seq data.
While conducting this project, the scientists also identified for the first time another cell type, called a subodontoblast, which they believe is a progenitor of odontoblasts, a cell type crucial for tooth formation. The researchers found that together these cell types could be induced to form small, three-dimensional, multicellular mini-organs called organoids.
These organised themselves into structures similar to those seen in developing human teeth and secreted three essential enamel proteins: ameloblastin, amelogenin and enamelin. These proteins would then form a matrix and a mineralisation process that is essential for forming enamel with the requisite hardness would follow.
One possibility is be to create enamel in the laboratory that could then be used to fill cavities and other defects. Ruohola-Baker points said another approach would be to create “living fillings” that could grow into and repair cavities and other defects. Ultimately, the goal would be to create stem cell-derived teeth that could replace lost teeth entirely.
“Many of the organs we would like to be able to replace, like human pancreas, kidney and brain, are large and complex,” said Ruohola-Baker. “Regenerating them safely from stem cells will take time.
“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.”