Molecular and cellular processes in salivary gland homeostasis and regeneration
Molecular and cellular processes in salivary gland homeostasis and regeneration
Saliva has essential digestive and protective oral functions and its supply is maintained by the salivary glands. Autoimmune diseases, medication side effects, and radiation for head and neck cancer, can permanently damage and reduce the function of the salivary glands. These can lead to an increase in mouth infections, caries, pain, swallowing and speech problems, causing social isolation and poor well-being. Currently, there are no curative therapies that can restore salivary gland function. Therefore, research of Paola Serrano Martinez has aimed at the development of a regenerative approach which requires to fully understand the identities of the stem cells in the salivary gland and the molecular cues driving their function.
For this understanding, we used organoid models which resemble the salivary gland composition and contain stem cells. At first, we developed a novel salivary gland organoid model. The use of this model to assess stem cell regeneration after irradiation revealed no differences in radiosensitivity between two major salivary glands. To identify new salivary gland stem cells, we explored the use of dormancy (quiescence), leading to the finding that active cycling cells maintain the salivary gland. Moreover, we identified that the Hippo and Notch signaling pathways differentially drive salivary gland balance and regeneration. Specifically, we found that the Notch pathway controls the dynamics of a specific population of salivary gland cells.
These results provide deeper insight into the cellular and molecular mechanisms driving salivary gland maintenance and regeneration, which could advance the development of a regenerative approach to help patients suffering from reduced salivary function.