Patients with cancers of the head and neck that have undergone radiation therapy often suffer from severe dry mouth (xerostomia) due to radiation-induced damage to the salivary glands. While current xerostomia therapies provide patients with temporary symptom relief, there are no treatments available to restore salivary gland function in these individuals. Nan Xiao and colleagues at Stanford University School of Medicine isolated submandibular glands from adult mice and identified a stem cell population in this tissue that that formed salispheres in vitro. Upon transplantation, these stem cells were able to incorporate into the secretory ducts of the submandibular gland and restore salivation in irradiated animals. Gene expression analysis revealed that these cells express high levels of glial cell line-derived neurotrophic factor (GDNF). Importantly, GDNF alone rescued saliva production in irradiated mice, but did not protect differentiated submandibular gland cells against radiation-mediated damage. In their companion Commentary, Adam Swick and Randall Kimple of the University of Wisconsin discuss how GDNF could potentially be used to improve xerostomia treatment. The accompanying image shows fluorescent staining a salisphere derived from murine submandibular gland stem cells. Embryonic stem cell marker keratin 5 (red) colocalizes with basal epithelial marker keratin 14 (green). Cell nuclei are labeled blue with DAPI.
Stem cell–based regenerative therapy is a promising treatment for head and neck cancer patients that suffer from chronic dry mouth (xerostomia) due to salivary gland injury from radiation therapy. Current xerostomia therapies only provide temporary symptom relief, while permanent restoration of salivary function is not currently feasible. Here, we identified and characterized a stem cell population from adult murine submandibular glands. Of the different cells isolated from the submandibular gland, this specific population, Lin–CD24+c-Kit+Sca1+, possessed the highest capacity for proliferation, self renewal, and differentiation during serial passage in vitro. Serial transplantations of this stem cell population into the submandibular gland of irradiated mice successfully restored saliva secretion and increased the number of functional acini. Gene-expression analysis revealed that glial cell line–derived neurotrophic factor (
Nan Xiao, Yuan Lin, Hongbin Cao, Davud Sirjani, Amato J. Giaccia, Albert C. Koong, Christina S. Kong, Maximilian Diehn, Quynh-Thu Le
Xerostomia, or dry mouth, is a common side effect of head and neck radiotherapy, Sjögren syndrome, diabetes, old age, and numerous medications. In this issue of the
Adam Swick, Randall J. Kimple