Scientists say they have taken a “critical first step” in developing a treatment that could allow people to regrow their lost or broken teeth. With further work, they hope this discovery could be used to create “living shavings” that grow and produce real enamel to regrow the tooth.
In a new study, researchers from the University of Washington created an organoid in the lab that was capable of producing the proteins that make up tooth enamel, the outer protective layer of teeth (and the hardest material in the human body).
This was achieved with the help of stem cells that were induced to become the specialized cells, called amyloblasts, that produce the enamel during tooth formation. These cells die after tooth formation is complete, leaving the adult body with no way to regenerate much-needed enamel.
But now, scientists have succeeded in creating amyloblasts in the laboratory, offering a possible way to overcome this problem.
“This is a critical first step toward our long-term goal of developing stem cell-based therapies to repair damaged teeth and regenerate those that have been lost,” said Hai Zhang, study co-author and professor of restorative dentistry at the University of Washington. he said to one statement.
The different colors in this image of enamel development show which genes are expressed at each stage of development.
Image credit: UW Dental Organoid Research Team
To get the “blueprint” of how to make amyloblasts, the team had to look at the silly genetics that underpin the creation of cells in the body. DNA is like a recipe book that contains the instructions for making all the proteins in our body. These instructions are delivered to the molecular machines that assemble proteins via RNA molecules, called messenger RNA (mRNA).
Throughout the numerous stages of development of any tissue, different proteins are needed at each stage, which is regulated through the activation and deactivation of genes. To recover the stage of enamel production, the team used a technique called “single-cell combinatorial RNA-sequencing (sci-RNA-seq).” A computer model was then used to understand how the pattern of gene activity manages to encode proteins that turn undifferentiated stem cells into fully differentiated amyloblasts.
The final product is a complex organoid: a tiny, three-dimensional, multicellular mini-organ in a Petri dish.
This could potentially lead to the development of so-called “living fillings” that could grow and repair cavities and other defects, explains Professor Hannele Ruohola-Baker, a world-leading expert in regenerative medicine at the University of Washington, who led the project. .
“Many of the organs we would like to be able to replace, such as the human pancreas, kidney and brain, are large and complex. Regenerating them safely from stem cells will take time,” said Ruohola-Baker. “Teeth on the other hand are much smaller and less complex. It’s probably the low-hanging fruit. It may take a while before we can regenerate them, but we can now see the steps we need to take to get there.”
A number of studies have recently boasted promising results in the field of tooth regeneration. A notable example is the work of scientists from Kyoto University who showed how a protein called USAG-1 restricts tooth growth in mice. By turning off the gene that codes for the production of the protein, the mice were able to regenerate their teeth freely. While the research from Japan is also in its early days, it has been suggested that human clinical trials could begin in 2024.
The study is published in the journal Developmental Cell.
