Concise Review: Adult Salivary Gland Stem Cells and a Potential Therapy for Xerostomia

Abstract

The ability to speak, swallow, masticate, taste food, and maintain a healthy oral cavity is heavily reliant on the presence of saliva, the hugely important effect of which on our everyday lives is often unappreciated. Hyposalivation, frequently experienced by people receiving radiation therapy for head and neck cancers, results in a plethora of symptoms whose combined effect can drastically reduce quality of life. Although artificial lubricants and drugs stimulating residual function are available to ameliorate the consequences of hyposalivation, their effects are at best transient. Such management techniques do not address the source of the problem: a lack of functional saliva-producing acinar cells, resulting from radiation-induced stem cell sterilization. Post-radiotherapy stimulation of cell proliferation only results in improved saliva secretion when part of the tissue has been spared or when the dose to the salivary gland (SG) remains below a certain level. Therefore, stem cell replacement therapy may be a good option to treat radiation-induced hyposalivation. Substantial progress has been made lately in the understanding of cell turnover in the SG, and the recent identification of stem and progenitor cell populations in the SG provides a basis for studies toward development of a stem cell-based therapy for xerostomia. Here, we review the current state of knowledge of SG stem cells and their potential for use in a cell-based therapy that may provide a more durable cure for hyposalivation.

Rescue Effects and Underlying Mechanisms of IntraglandShhGene Delivery on Irradiation-Induced Hyposalivation

“…It was widely believed that acinar cells of the salivary gland are replaced through stem cell differentiation, 36 but one study has demonstrated that acinar cell proliferation accounts for postnatal growth and expansion of the salivary gland, as well as for maintenance and regeneration of the adult organ. 27 Similar mechanisms have been reported for the growth and maintenance of other glands in the digestive tract including liver and pancreas.…”

Radiation Induced Xerostomia: Current Concepts and Future Trends

“…Kinase inhibitors (Roscovitine) have been found to suppress apoptosis and temporarily inhibit cell cycle progression (G2/M cell cycle) to allow for DNA repair 16 . Ligating the main excretory duct is reported to cause proliferation of ductal cells, key to which would be the number of surviving stem/progenitor cells 17 . Ascl3+ progenitor cells were identified in developing rat submandibular glands.…”

Salivary Glands

“…In fact, analysis in the mouse SMG yielded the conclusion that "most, if not all, proliferative activity leading to acinar cell population maintenance occurs by self-proliferation" (Denny et al 1993). Despite this convincing body of evidence, as stem cells moved to central stage, the idea that salivary glands are maintained by stem cells became accepted (Pringle et al 2013). It is thus important to clarify the role of both stem cells and differentiated cells in maintaining the salivary glands.…”

“…The design of restorative therapies requires knowledge of how the salivary glands normally replace aging cells or repair damaged tissue. The prevailing view is that new secretory acinar and duct cells are generated from resident adult stem cells (reviewed in Pringle et al 2013). However, the relative contributions of stem cells to salivary gland cell turnover have been unclear.…”