Human salivary gland stem/progenitor cells remain dormant even after irradiation

Progressive loss of salivary gland function occurs in most patients undergoing head and neck radiotherapy. It is unclear whether adult salivary gland tissue contains stem/progenitor cells. In this study, we used a colony assay to clarify the presence of stem/progenitor cells in adult submandibular glands after irradiation. We developed a novel culture system that promotes single-cell colony formation with low density culture of irradiated and non-irradiated adult human submandibular gland cells using serum-free medium following serum-supplemented medium. The cells from all samples, except those obtained from the oldest patient who received the highest radiation dose, expressed acinar, ductal, and myoepithelial cell-lineage markers with reverse transcription-polymerase chain reaction (RT-PCR) and immunostaining. A sub-culture of these colonies with serum-free medium showed high multipotency. These results are the first description of presence of salivary gland stem/progenitor cells with self-renewal, high proliferation and multipotent differentiation activity in salivary glands, even after irradiation. The survival of the cells depends on radiation dose and cell aging.