Organoids have now been created from stem cells to secrete the proteins that form dental enamel, the substance that protects teeth from damage and decay. Tooth enamel protects teeth from the mechanical stresses incurred by chewing and helps them resist decay.
Enamel is made during tooth formation by specialised 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 subject to loss.
To create ameloblasts in the laboratory, Researchers from the University of Washington first had to understand the genetic programme that drives foetal stem cells to develop into these highly specialised enamel-producing cells. To do this, they used a technique called single-cell combinatorial indexing RNA sequencing (sci-RNA-seq), revealing what 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.
The researchers 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.
While conducting this project, the scientists also identified another cell type called a subodontoblast for the first time, which they believe is a progenitor of odontoblasts, a cell type crucial for tooth formation.
The researchers found that 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 mineralisation process that is essential for forming enamel.
The research team now hopes to refine the process to make enamel comparable in durability to that found in natural teeth and develop ways to use this enamel to restore damaged teeth.