Chen Yi-Xing, Zeng Zhao-Chong, Sun Jing, Zeng Hai-Ying, Huang Yan-, Zhang Zhen-Yu
Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
J Radiat Res. 2015 Jul;56(4):700-8. doi: 10.1093/jrr/rrv026. Epub 2015 Jun 11.
Current management of radiation-induced liver injury is limited. Sinusoidal endothelial cell (SEC) apoptosis and inflammation are considered to be initiating events in hepatic damage. We hypothesized that mesenchymal stem cells (MSCs) possess anti-apoptotic and anti-inflammatory actions during hepatic irradiation, acting via paracrine mechanisms. This study aims to examine whether MSC-derived bioactive components are protective against radiation-induced liver injury in rats. MSC-conditioned medium (MSC-CM) was generated from rat bone marrow-derived MSCs. The effect of MSC-CM on the viability of irradiated SECs was examined by flow cytometric analysis. Activation of the Akt and ERK pathways was analyzed by western blot. MSC-CM was also delivered to Sprague-Dawley rats immediately before receiving liver irradiation, followed by testing for pathological features, changes in serum hyaluronic acid, ALT, and inflammatory cytokine levels, and liver cell apoptosis. MSC-CM enhanced the viability of irradiated SECs in vitro and induced Akt and ERK phosphorylation in these cells. Infusion of MSC-CM immediately before liver irradiation provided a significant anti-apoptotic effect on SECs and improved the histopathological features of injury in the irradiated liver. MSC-CM also reduced the secretion and expression of inflammatory cytokines and increased the expression of anti-inflammatory cytokines. MSC-derived bioactive components could be a novel therapeutic approach for treating radiation-induced liver injury.
目前对放射性肝损伤的治疗方法有限。肝血窦内皮细胞(SEC)凋亡和炎症被认为是肝损伤的起始事件。我们假设间充质干细胞(MSC)在肝脏辐射期间具有抗凋亡和抗炎作用,通过旁分泌机制发挥作用。本研究旨在探讨MSC衍生的生物活性成分是否对大鼠放射性肝损伤具有保护作用。MSC条件培养基(MSC-CM)由大鼠骨髓来源的MSC产生。通过流式细胞术分析检测MSC-CM对受辐照SEC活力的影响。通过蛋白质免疫印迹法分析Akt和ERK信号通路的激活情况。在接受肝脏照射前,将MSC-CM立即注入Sprague-Dawley大鼠体内,随后检测病理特征、血清透明质酸、谷丙转氨酶(ALT)和炎性细胞因子水平的变化以及肝细胞凋亡情况。MSC-CM在体外增强了受辐照SEC的活力,并诱导这些细胞中的Akt和ERK磷酸化。在肝脏照射前立即注入MSC-CM对SEC具有显著的抗凋亡作用,并改善了受辐照肝脏的损伤组织病理学特征。MSC-CM还减少了炎性细胞因子的分泌和表达,并增加了抗炎细胞因子的表达。MSC衍生的生物活性成分可能是治疗放射性肝损伤的一种新的治疗方法。