Regeneration of Radiation Damaged Salivary Glands with Adipose-Derived Stromal Cells

Objectives: Radiotherapy is one of the most effective treatments for head and neck cancer. However, the development of dry mouth syndrome is an unavoidable side effect because, in addition to the tumor, the normal salivary glands are included in the irradiation field. Previously, we investigated the protective efficacy of basic fibroblast growth factor (bFGF) in radiation-damaged salivary glands. In this study, we investigated the efficacy of adipose-derived stromal cell (ADSC) transplantation for the regeneration of radiation damaged salivary glands. Study Design: Prospective animal experiment with control. Methods: ADSCs (500,000 cells isolated from green fluorescent protein mice) were transplanted into submandibular glands of C57BL/6 mice 10 weeks after 10 Gy irradiation (ADSC group). Phosphate-buffered saline was administered to mice as a control (sham group). Submandibular gland morphology and saliva flow rate were assessed just prior to transplantation and at 5 and 10 weeks posttransplantation. Quantitative RT-PCR was performed to examine the response of irradiated submandibular glands to ADSC transplantation. Results: Saliva flow rate in the ADSC group was improved compared to the sham group. Although acinar cell damage was detected in both groups, the proliferation of blood vessels and other paracrine effects were observed only in the ADSC group. Additionally, the differentiation of ADSCs into blood endothelial cells and ductal cells was also observed. Conclusions: Our study indicates that ADSCs have the potential to restore salivary gland function after irradiation. The restoration of blood flow within submandibular gland tissue may explain the beneficial effects of ADSCs.