Regeneration of irradiated salivary glands by stem cell therapy

Yearly, worldwide more than 500.000 new head and neck cancer patients are treated with radiotherapy. Co-irradiation of salivary glands may lead to xerostomia (=dry mouth syndrome), resulting in permanent loss of saliva production. This loss of gland function after radiation is thought to be due to a loss of stem cells that are no longer able to replenish saliva-producing acinar cells. Therefore, stem cell therapy could be utilized to prevent radiation-induced damage to the salivary gland. Bone marrow-derived (stem) cells (BMCs), when mobilized to the blood circulation, are able to contribute to the regeneration of acinar cells and blood vessels of irradiated mice salivary glands, resulting in increasing saliva production. Since only low percentages of acinar cells were BM-derived, the engrafted BMCs seem to secrete micro-environmental factors which stimulate radiation-surviving salivary gland stem/progenitor cells. Optimal recovery of irradiated salivary glands could possibly be obtained by increasing functional salivary gland stem cell numbers. This was accomplished by in vivo administration of Keratinocyte Growth Factor, which resulted in the formation of almost normal levels of acinar cell numbers and saliva production. A more clinical application could be obtained by transplanting in vitro cultured, characterized and isolated salivary gland stem cells. Serial transplantation of stem cells, expressing c-Kit, in irradiated salivary glands resulted in both functional as morphological improvement of damaged glands. Further, c-Kit+ cells could also be isolated from human salivary glands, which open perspectives for potential clinical stem cell transplantations post-irradiation. The concept of stem cell therapy, i.e. increasing the number of stem cell numbers via growth factors or via stem cell transplantations, could lead to a novel approach to prevent radiation-induced damage to normal organs, which is not necessarily limited to salivary glands.