Xu Wenda, Chen Jiang, Liu Xu, Li Hongyu, Qi Xingshun, Guo Xiaozhong
Department of Gastroenterology, The 251st Hospital of PLA, Zhangjiakou, China.
Department of Gastroenterology, Shenyang General Hospital of PLA, Shenyang, China.
Transl Res. 2016 May;171:38-51. doi: 10.1016/j.trsl.2015.12.010. Epub 2015 Dec 19.
Radiation enteritis is one of the most common complications of cancer radiotherapy, and the development of new and effective measures for its prevention and treatment is of great importance. Adult bone marrow stromal stem cells (ABMSCs) are capable of self-renewal and exhibit low immunogenicity. In this study, we investigated ABMSC transplantation as a treatment for acute radiation enteritis. We developed a dog model of acute radiation enteritis using abdominal intensity-modulated radiation therapy in a single X-ray dose of 14 Gy. ABMSCs were cultured in vitro, identified via immunofluorescence and flow cytometry, and double labeled with CM-Dil and superparamagnetic iron oxide (SPIO) before transplantation, which took place 48 hours after abdominal irradiation in a single fraction. The dog model of acute radiation enteritis was transplanted with cultured ABMSCs labeled with CM-Dil and SPIO into the mesenteric artery through the femoral artery. Compared with untreated control groups, dogs treated with ABMSCs exhibited substantially longer survival time and improved relief of clinical symptoms. ABMSC transplantation induced the regeneration of the intestinal epithelium and the recovery of intestinal function. Furthermore, ABMSC transplantation resulted in elevated serum levels of the anti-inflammatory cytokine interleukin-11 (IL10) and intestinal radioprotective factors, such as keratinocyte growth factor, basic fibroblast growth factor-2, and platelet-derived growth factor-B while reducing the serum level of the inflammatory cytokine IL17. ABMSCs induced the regeneration of the intestinal epithelium and regulated the secretion of serum cytokines and the expression of radioprotective proteins and thus could be beneficial in the development of novel and effective mitigators of and protectors against acute radiation enteritis.
放射性肠炎是癌症放射治疗最常见的并发症之一，开发新的有效防治措施具有重要意义。成人骨髓基质干细胞（ABMSCs）能够自我更新，且免疫原性低。在本研究中，我们研究了ABMSC移植作为急性放射性肠炎的一种治疗方法。我们使用腹部调强放射治疗，单次X射线剂量为14 Gy，建立了急性放射性肠炎的犬模型。ABMSCs在体外培养，通过免疫荧光和流式细胞术进行鉴定，并在移植前用CM-Dil和超顺磁性氧化铁（SPIO）进行双重标记，移植在腹部单次照射后48小时进行。将用CM-Dil和SPIO标记的培养ABMSCs通过股动脉移植到急性放射性肠炎犬模型的肠系膜动脉中。与未治疗的对照组相比，接受ABMSCs治疗的犬存活时间显著延长，临床症状缓解情况有所改善。ABMSC移植诱导了肠上皮再生和肠功能恢复。此外，ABMSC移植导致抗炎细胞因子白细胞介素-11（IL10）和肠道辐射保护因子（如角质形成细胞生长因子、碱性成纤维细胞生长因子-2和血小板衍生生长因子-B）的血清水平升高，同时降低了炎性细胞因子IL17的血清水平。ABMSCs诱导了肠上皮再生，调节了血清细胞因子的分泌以及辐射保护蛋白的表达，因此可能有助于开发新型有效的急性放射性肠炎缓解剂和保护剂。
