Department of Otorhinolaryngology - Head and Neck Surgery, Inha University School of Medicine, Incheon, Republic of Korea.
Oral Oncol. 2013 Feb;49(2):136-43. doi: 10.1016/j.oraloncology.2012.08.010. Epub 2012 Sep 13.
External irradiation in head and neck cancers may induce irreversible hyposalivation and consequent xerostomia, stemming from radiation damage to salivary glands (SGs). As cell-based therapy has been reported to be able to repair or restore damaged SG tissues, we attempted to determine whether bone marrow-derived clonal mesenchymal stem cells (BM-cMSCs) can ameliorate irradiation-induced salivary gland damage via a murine model.
External irradiation at a dose of 15Gy was delivered to the neck fields of C57BL/6 mice. We directly administered either homologous mouse BM-cMSCs labeled with PKH26 (treatment group) or PBS (control group) into SGs 24h after irradiation. Salivary flow rate (SFR) and lag time of salivation were measured at 12weeks after transplantation. At 4 and 12weeks post-transplantation, we performed morphological, histological, and immunofluorescent examinations. Transdifferentiation of administered BM-cMSCs into salivary epithelial cells was observed by confocal microscopy.
SFR was significantly increased in BM-cMSCs-transplanted mice compared with PBS-injected mice at 12weeks after transplantation. Administration of BM-cMSCs preserved the microscopic morphologies of SGs, with more functional acini in BM-cMSC-transplanted SGs than in PBS-injected SGs. Immunofluorescent staining revealed less apoptotic cells and increased microvessel density in BM-cMSC-transplanted SGs compared with PBS-injected SGs. PKH-26 labeled BM-cMSCs were detected in transplanted SGs at 4weeks after transplantation and in vivo transdifferentiation of BM-cMSCs into acinar cells was also observed.
This study suggests that BM-cMSCs can ameliorate salivary damage following irradiation and can be used as a source of cell-based therapy for restoration of irradiation-induced salivary hypofunction.
头颈部癌症的外部放射治疗可能会导致唾液腺（SGs）辐射损伤引起的不可逆转的低分泌和随后的口干。由于细胞疗法已被报道能够修复或恢复受损的 SG 组织，我们试图通过小鼠模型确定骨髓来源的克隆间充质干细胞（BM-cMSCs）是否可以改善辐射引起的唾液腺损伤。
在 C57BL/6 小鼠颈部区域给予 15Gy 的外部照射。照射后 24 小时，我们直接将标记有 PKH26 的同源小鼠 BM-cMSCs（治疗组）或 PBS（对照组）注入 SG 中。在移植后 12 周测量唾液流量（SFR）和唾液分泌潜伏期。在移植后 4 和 12 周，我们进行了形态学、组织学和免疫荧光检查。通过共聚焦显微镜观察给药的 BM-cMSCs 向唾液上皮细胞的转分化。
与 PBS 注射组相比，BM-cMSCs 移植组在移植后 12 周时 SFR 显著增加。BM-cMSC 给药保存了 SG 的微观形态，BM-cMSC 移植 SG 中的功能性腺泡比 PBS 注射 SG 中的更多。免疫荧光染色显示 BM-cMSC 移植 SG 中的凋亡细胞较少，微血管密度增加，与 PBS 注射 SG 相比。在移植后 4 周时在移植的 SG 中检测到 PKH-26 标记的 BM-cMSCs，并且还观察到 BM-cMSCs 在体内向腺泡细胞的转分化。
本研究表明 BM-cMSCs 可以改善照射后的唾液损伤，并可用作基于细胞的治疗的来源，以恢复照射引起的唾液功能减退。
