Department of Nutritional Sciences, University of Arizona, Tucson, Arizona, United States of America.
Department of Biomedical Engineering, University of Arizona, Tucson, Arizona, United States of America.
PLoS One. 2018 Mar 28;13(3):e0193942. doi: 10.1371/journal.pone.0193942. eCollection 2018.
Worldwide, 500,000 cases of head and neck cancer (HNC) are reported each year and the primary treatment for HNC is radiotherapy. Although the goal of radiotherapy is to target the tumor, secondary exposure occurs in surrounding normal tissues, such as the salivary glands. As a result, despite successful treatment of the cancer, patients are left with long-term side effects due to direct damage to the salivary glands. The effect is chronic and currently there is no treatment. Stem cells are an attractive therapeutic option for treatment of radiation-induced glandular dysfunction because of the potential to regenerate damaged cell populations and restore salivary gland function. However, limited knowledge about the endogenous stem cell population post irradiation hinders the development for stem cell-based therapies. In this study, an ex vivo sphere formation cell culture system was utilized to assess the self-renewal capacity of cells derived from parotid salivary glands at a chronic time point following radiation. Salivary glands from irradiated mice generate significantly fewer salispheres, but can be stimulated with fetal bovine serum (FBS) to generate an equivalent number of salispheres as unirradiated salivary glands. Interestingly, the number and size of salispheres formed is dependent on the concentration of FBS supplemented into the media. Salispheres derived from irradiated glands and cultured in FBS media were found to contain cells that proliferate and express progenitor and acinar cell markers such as Keratin 5, Keratin 14, Aquaporin 5, and NKCC1. Utilization of insulin-like growth factor (IGF1) injections following radiation treatment restores salivary gland function and improves salisphere generation. These findings indicate that stimulation of these cellular populations may provide a promising avenue for the development of cell-based therapies for radiation-induced salivary gland damage.
全世界每年报告有 50 万例头颈部癌症（HNC）病例，HNC 的主要治疗方法是放射治疗。尽管放射治疗的目的是针对肿瘤，但二次照射会发生在周围的正常组织中，如唾液腺。因此，尽管癌症得到了成功的治疗，但由于直接损伤唾液腺，患者会留下长期的副作用。这种影响是慢性的，目前尚无治疗方法。干细胞是治疗放射性腺体功能障碍的一种有吸引力的治疗选择，因为它有可能再生受损的细胞群并恢复唾液腺功能。然而，由于对辐照后内源性干细胞群体的了解有限，阻碍了基于干细胞的治疗方法的发展。在这项研究中，利用体外球体形成细胞培养系统来评估辐射后慢性时间点来源于腮腺唾液腺的细胞的自我更新能力。辐照小鼠的唾液腺产生的唾液球体明显减少，但可以用胎牛血清（FBS）刺激产生与未辐照唾液腺相同数量的唾液球体。有趣的是，形成的唾液球体的数量和大小取决于补充到培养基中的 FBS 浓度。在 FBS 培养基中培养的来自辐照腺体的唾液球体中发现含有增殖的细胞，并表达祖细胞和腺泡细胞标志物，如角蛋白 5、角蛋白 14、水通道蛋白 5 和 NKCC1。在放射治疗后使用胰岛素样生长因子（IGF1）注射可恢复唾液腺功能并增加唾液球体的生成。这些发现表明，刺激这些细胞群体可能为开发基于细胞的治疗放射性唾液腺损伤提供有前途的途径。
