Salivary gland stem cells

The salivary glands of patients with head and neck cancer, who receive radiotherapy, are often unavoidably exposed to radiation. The resulting damage impairs the function of the salivary glands leading to irreversible dry mouth syndrome (xerostomia), which induces a severe life-long loss of quality of life. Currently no adequate treatments are available for xerostomia. Salivary gland stem cell therapy is an attractive putative option to salvage these patients. Moreover, such adult stem cells do not have the ethical or transformation problems associated with embryonic stem cells and induced pluripotent stem cells, respectively. However, the low number of salivary gland stem cells that can be obtained from the tissue impedes application.

To develop such an adult stem therapy, first stem cells of salivary glands need to be isolated, identified, characterized and potentially expanded. In this thesis, we report the identification, characterization and functional potential of rodent salivary glands. We have identified murine CD24hi/CD29hi expressing cells as potential stem cells by showing in vitro single cell based self-renewal and differentiation into organoids that are defined properties of adult stem cells. Moreover, we were able to unprecedentedly expand and concomitantly enrich into full functional adult stem cells, capable to potently functionally restore radiation damage of the mouse salivary gland. The research reported in this thesis brings the development of an adult stem cell therapy for patients suffering from xerostomia closer to the clinic with the aim to restore their quality of life.