Enamel, formed by ameloblast cells, is the hardest substance in human body, and the first defensive line for healthy tooth. Unfortunately, nearly 40% the incisor teeth in babies and children have some sort of enamel defect. To replace enamel, or even entire teeth, we need strategies to regenerate the cells that originally make enamel, the ameloblasts, as these cells do not exist after tooth formation is complete.
The researchers from COR are exploring two strategies to address this challenge. One of these strategies is to re-engineer dental pulp stem cells, which can be isolated from the pulp tissue of extracted teeth, to an earlier differentiation stage when these cells can direct non-dental epithelial cells and tissues form ameloblasts and enamel of teeth. We are also exploring strategies to understand the transcriptional regulation of secretory ameloblasts. We have identified a master transcriptional regulator, special AT-rich sequence-binding protein-1 (SATB1) that is critical for ameloblast differentiation. We anticipate that SATB1, along with a few other key transcription factors, can be used to transform human embryonic stem cells or induced pluripotent stem cells (IPS) derived from somatic cells, to ameloblasts.
A NIH R01 grant to fund basic research focusing on the function of SATB1 in ameloblast differentiation was recently awarded to Dr. Yan Zhang, MD, PhD.
Image: Strategies are being developed to pave the way to differentiate non-dental epithelial cells into polarized and amelogenin producing secretory ameloblasts (SAB), which are the cells that make the enamel matrix (e)