Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Laryngoscope. 2011 Sep;121(9):1864-9. doi: 10.1002/lary.22080. Epub 2011 Jul 11.
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.
Prospective animal experiment with control.
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.
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.
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.
放射疗法是治疗头颈部癌症最有效的方法之一。然而,口干症是一种不可避免的副作用,因为除了肿瘤,正常的唾液腺也包含在照射野内。以前,我们研究了碱性成纤维细胞生长因子(bFGF)对放射损伤唾液腺的保护作用。在这项研究中,我们研究了脂肪来源的基质细胞(ADSC)移植对辐射损伤唾液腺再生的疗效。
有对照的前瞻性动物实验。
在 10 Gy 照射后 10 周,将分离自绿色荧光蛋白小鼠的 500,000 个 ADSC(ADSC 组)移植到 C57BL/6 小鼠的颌下腺中。向小鼠注射磷酸盐缓冲液作为对照(假手术组)。在移植前和移植后 5 周和 10 周评估颌下腺形态和唾液流量。通过定量 RT-PCR 检查照射后的颌下腺对 ADSC 移植的反应。
与假手术组相比,ADSC 组的唾液流量得到改善。虽然在两组中都检测到腺泡细胞损伤,但仅在 ADSC 组观察到血管增殖和其他旁分泌作用。此外,还观察到 ADSC 分化为血内皮细胞和导管细胞。
我们的研究表明,ADSC 有可能在照射后恢复唾液腺功能。颌下腺组织内血流的恢复可能解释了 ADSC 的有益作用。