FRIDAY, Aug. 18, 2023 (HealthDay News) — Damaged teeth could one day be repaired with “living fillings” made from stem cells, a new study reports.
In the lab, the researchers induced the stem cells to form small, multicellular mini-organs that secrete the proteins that make up tooth enamel, according to a report published Aug. 14 in the journal Developmental Cell.
“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,” co-author Dr. Hai Zhangprofessor of restorative dentistry at the University of Washington School of Dentistry, said in a school news release.
Tooth enamel is the hardest tissue in the human body. It protects teeth from the mechanical stresses of chewing and helps them resist tooth decay, the researchers said in background notes.
Enamel is produced during tooth formation by special cells called amyloblasts. The cells die when the teeth stop growing, leaving no room for the body to repair or regenerate the damaged enamel.
The aim of this research was to create amyloblasts in the laboratory.
For starters, the researchers used RNA sequencing to understand why some embryonic stem cells develop into these highly specialized enamel-producing cells.
Through this sequencing, they created a series of “snapshots” that tracked each stage of cell development as well as the genes that are active at those stages.
Computer analysis then calculated the likely sequence of gene activities that would have to occur for stem cells to develop into ameloblasts.
“The computer program predicts how to get from here to there, the road map, the plan needed to make amyloblasts,” said project leader Hannele Ruohola-Bakerprofessor of biochemistry and associate director of the UW Medicine Institute for Stem Cell and Regenerative Medicine.
Following the path blazed by computer analysis, the researchers after much trial and error led undifferentiated human stem cells to become amyloblasts.
They did this by using chemical signals that activated different genes in the stem cells, mimicking the course of natural development.
The researchers also identified for the first time a type of tooth cell called subodontoblasts, which appears to be a precursor to odontoblasts, a cell type vital to tooth formation.
Together, as they developed, the cells formed small, three-dimensional, multicellular mini-organs called organoids.
These organelles assembled into structures similar to those seen in developing human teeth and began to secrete three proteins essential for enamel: ameloblastin, amelogenin, and enamel.
The proteins then began to form and mineralize, a step necessary for the formation of hard tooth enamel.
By improving the process, the research team hopes to make an enamel as durable as that found in natural teeth and then develop ways to use that enamel to repair damaged teeth, Zhang said.
Enamel created in the lab could one day be used to fill cavities and other defects. An even more ambitious goal would be to create “living fillings” that would augment and repair cavities, Ruohola-Baker said in the release.
Such “living fillings” could even be used to grow teeth derived from stem cells that could completely replace lost teeth.
“This may ultimately be the ‘Century of Living Seals’ and human regenerative dentistry in general,” Ruohola-Baker added.
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SOURCE: University of Washington School of Medicine, news release, August 14, 2023