Soluble Notch Agonist Enables Human Ameloblast Maturation and Enamel-like Tissue Formation for Tooth Regeneration

However, over 90% of adults have lost or damaged enamel and cannot regenerate the protective structure due to lack of enamel producing cells, ameloblasts. iPSC derived secretory Ameloblasts (isAM) have promise in future regenerative dentistry. Today it is not known why iAM maturation requires intimate contact with the dentin producing cell type, odontoblast.

Here we reveal that one of the critical signaling ligands emanating from odontoblasts for ameloblast maturation is Delta, the ligand for Notch receptor. We showed that our designed, soluble Notch agonist can induce iAM organoid maturation in an unprecedented manner, without interactions with odontoblast layer. Notably, soluble Notch agonist induces the iAM maturation to a novel, WDR72 positive mature secretory AM stage (ismAM) in our ameloblast organoid model.