Stem Cells Used to Respectively Regenrate Teeth Enamel and Its Advantages

Thursday - August 17 2023, 02:42 UTC - 1 year ago

Researchers from the University of Washington in Seattle used stem cells to produce organoids that release the proteins responsible for forming dental enamel and opened up possibilities of manipulating stem cells to reconstruct and regenerate damaged teeth.

Stem cells have been used to produce organoids that release the proteins responsible for forming dental enamel, a substance that shields teeth from harm and decay. This initiative was led by a multi-disciplinary team of researchers from the University of Washington in Seattle.

"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," said Hai Zhang, professor of restorative dentistry at the UW School of Dentistry and one of the co–authors of the paper describing the research.

The findings are published today in the journal Developmental Cell. Ammar Alghadeer, a graduate student in Hannele Ruohola-Baker’s laboratory in the Department of Biochemistry at the UW School of Medicine was the lead author on the paper. The lab is affiliated with the UW Medicine Institute for Stem Cell and Regenerative Medicine.

The researchers explained that tooth enamel protects teeth from the mechanical stresses incurred by chewing and helps them resist decay. It is the hardest tissue in the human body.

Enamel is made during tooth formation by specialized cells called ameloblasts. When tooth formation is complete, these cells die off. Consequently, the body has no way to repair or regenerate damaged enamel, and teeth can become prone to fractures or be subject to loss.

To create ameloblasts in the laboratory, the researchers first had to understand the genetic program that drives fetal stem cells to develop into these highly specialized enamel-producing cells.

To do this 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.

This is possible because RNA molecules, called messenger RNA (mRNA), carry the instructions for proteins encoded in the DNA of activated genes to the molecular machines that assemble proteins. That is why changes in the levels of mRNA at different stages of a cell’s development reveal which genes are turned on and off at each stage.

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 sophisticated computer program, called Monocle, 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 Ruohola-Baker, who headed the project. She is a professor of biochemistry and associate director of the UW Medicine Institute for Stem Cell and Regenerative Medicine.

With this trajectory mapped out, the researchers, after much trial and error, were able to coax undifferentiated human stem cells into becoming ameloblasts. They did this 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. In some cases, they used known chemical signals. In other cases, collaboraEach team member had different expertise, each of which was essential to the success of the endeavor. Zhang is a Howard Hughes Medical Institute Investigator and senior professor in the Department of Restorative Dentistry at the UW School of Dentistry. Ruohola-Baker is a professor of biochemistry in the UW School of Medicine, associate director of the UW Medicine Institute for Stem Cell and Regenerative Medicine, and an affiliate professor at the UW School of Dentistry.

With their work, the researchers demonstrated how to push stem cells down a defined path to become functional ameloblasts in the laboratory. It could open up the possibility of manipulating stem cells to reconstruct and regenerate damaged teeth and essentially bring back that lost function with a predictable outcome.

"This was truly a team effort, and it was the great collaborations between the group that made this work possible," Alghadeer said. "Having the amazing support from Drs. Zhang and Ruohola-Baker, and access to their laboratories, allowed us to work on this challenging project." .