Salivary gland stem cells: A review of development, regeneration and cancer

Abstract

Salivary glands are responsible for maintaining the health of the oral cavity and are routinely damaged by therapeutic radiation for head and neck cancer as well as by autoimmune diseases such as Sjögren's syndrome. Regenerative approaches based on the reactivation of endogenous stem cells or the transplant of exogenous stem cells hold substantial promise in restoring the structure and function of these organs to improve patient quality of life. However, these approaches have been hampered by a lack of knowledge on the identity of salivary stem cell populations and their regulators. In this review we discuss our current knowledge on salivary stem cells and their regulators during organ development, homeostasis and regeneration. As increasing evidence in other systems suggests that progenitor cells may be a source of cancer, we also review whether these same salivary stem cells may also be cancer initiating cells.

Deciphering Molecular and Phenotypic Changes Associated with Early Autoimmune Disease in the Aire-Deficient Mouse Model of Sjögren’s Syndrome

“…Peripheral innervation is known to be essential to salivary gland homeostasis through the maintenance and activation of stem cells [ 22 ]. Although this specific role has not been evaluated in the LG, similar to the salivary gland, previous studies have shown that atrophy of LG acini occurs in the absence of a nerve supply [ 23 ].…”

GPR55 controls functional differentiation of self-renewing epithelial progenitors for salivation

“…We sought to address if increased cell proliferation accounts for salivary gland enlargement in Gpr55 -/mice by immunostaining for Ki67, a marker of cell proliferation (35), and we found significantly increased density/number of Ki67 + nuclei per granulated duct in Gpr55 -/mice of both sexes relative to WT littermates ( Figure 5, D and E, and Supplemental Figure 5, E-H). In addition, quantification of epithelial progenitor markers, such as SOX2 and SOX10 (36), members of the SRY-box family of transcription factors, revealed significant increases in immunoreactive nuclei in the submandibular and parotid gland of Gpr55 -/mice, suggesting life-long excess in cell proliferation ( Figure 5, F and G). Cleaved caspase-3 + cells, marking apoptosis (37), showed no significant difference between Gpr55 -/and WT mice (data not shown), making the contribution of disproportionate death rates to the salivary gland phenotype unlikely.…”

Advances in regenerative medicine for otolaryngology/head and neck surgery

“…Hyposalivation, one of the characteristics of xerostomia or dry mouth, can occur in patients with Sjögren’s syndrome or other autoimmune disorders, in patients with a history of head and neck radiation, or as a result of polypharmacy. Saliva production comes primarily from three pairs of major glands (parotid, submandibular, and sublingual), as well as more than 1000 minor glands in the upper aerodigestive tract 109…”