Chen Wei, Ju Songwen, Lu Ting, Xu Yongfang, Zheng Xiaocui, Wang Haiyan, Ge Yan, Ju Songguang
Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou 215000, China.
Suzhou Digestive Diseases and Nutrition Research Center, Affiliated Suzhou Hospital of Nanjing Medical University, North District of Suzhou Municipal Hospital, Suzhou 215008, China.
Cytokine. 2017 Jul;95:27-34. doi: 10.1016/j.cyto.2017.02.004. Epub 2017 Feb 20.
Radiation-induced intestinal injury (RIII) commonly occurs in patients who received radiotherapy for pelvic or abdominal cancer, or who suffered from whole-body irradiation during a nuclear accident. RIII can lead to intestinal disorders and even death given its integrity damage that results from intestinal stem cell (ISC) loss. Recovery from RIII relies on the intensity of supportive treatment, which can attenuate lethal infection and give surviving stem cells an opportunity to regenerate. It has been reported that RSPO1 is a cytokine with potent and specific proliferative effects on intestinal crypt cells. MSCs have multiple RIII-healing effects, including anti-inflammatory and anti-irradiation injury properties, due to its negative immune regulation and its homing ability to the damaged intestinal epithelia. To combine the comprehensive anti-injury potential of MSCs, and the potent ability of RSPO1 as a mitogenic factor for ISCs, we constructed RSPO1-modified C3H10 T1/2 cells and expected that RSPO1, the ISC-proliferative cytokine, could be delivered to the site of injury in a targeted manner. In this study, we transferred C3H10/RSPO1 intravenously via the retro-orbital sinus into mice suffering from abdominal irradiation at lethal dosages. Our findings demonstrated that C3H10/RSPO1 cells are able to directionally migrate to the injury site; enhance ISC survival, proliferation, and differentiation; and effectively repair the radiation-damaged intestinal epithelial cells. This study suggests that the directional delivery of RSPO1 by MSCs is a promising strategy to ameliorate, and even cure, RIII.
放射性肠损伤（RIII）常见于接受盆腔或腹部癌症放疗的患者，或在核事故中遭受全身照射的患者。由于肠干细胞（ISC）丢失导致肠完整性受损，RIII可导致肠道功能紊乱甚至死亡。RIII的恢复依赖于支持治疗的强度，支持治疗可减轻致命感染，并为存活的干细胞提供再生机会。据报道，RSPO1是一种对肠隐窝细胞具有强大而特异增殖作用的细胞因子。间充质干细胞（MSCs）具有多种促进RIII愈合的作用，包括抗炎和抗辐射损伤特性，这归因于其负性免疫调节作用及其向受损肠上皮的归巢能力。为了结合MSCs的综合抗损伤潜能以及RSPO1作为ISC促有丝分裂因子的强大能力，我们构建了RSPO1修饰的C3H10 T1/2细胞，并期望将ISC增殖细胞因子RSPO1以靶向方式递送至损伤部位。在本研究中，我们通过眶后窦将C3H10/RSPO1静脉注射到接受致死剂量腹部照射的小鼠体内。我们的研究结果表明，C3H10/RSPO1细胞能够定向迁移至损伤部位；提高ISC的存活、增殖和分化能力；并有效修复辐射损伤的肠上皮细胞。本研究表明，MSCs定向递送RSPO1是改善甚至治愈RIII的一种有前景的策略。
