Fang Chi-hua, Liu Sheng-jun, Chen Xiao-wu, Cui Bing, Wang Yan, Huang Zhi-rong
Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Zhonghua Wai Ke Za Zhi. 2007 May 1;45(9):598-601.
To study the location, immigration of allogenic grafted Feridex-labeled rat bone marrow stem cells (BMSCs) in chemically-induced acute injured livers and their role on repairing the injured liver function.
The rat models of chemically-induced acute hepatic injury established with CCl4 Feridex-labeled BMSCs were injected into the injured livers. Magnetic resonance imaging (MRI) examination was conducted on rat livers, the levels of ALT, AST and Fe3+ in the serum and hepatic tissues were studied 6 h before and 6 h, 1 w and 5 w after injection.
Cellular necrosis, congestion in the hepatic sinusoid and infiltration of inflammatory cells were seen in the model livers. Above 90 percent of the cells were Feridex-labeled BMSCs positive by prussian blue staining and iron particles were found in their endochylema through electron microscopy. MRI examination at the sequence of SE-T2WI showed remarkably low signal changes 6 h after injecting Feridex-labeled BMSCs and the site with signal changes gradually expanded 1 and 5 w after injection. Comparatively, the changes of low signal images at each time point in the injured livers were more obvious than those of the controls at all time points, respectively. Simultaneously, pathological injuries in the livers were ameliorated and the levels of ALT and AST in serums declined: these changes in the Feridex-labeled BMSCs group were more obvious than those in the non-Feridex-labeled BMSCs group. Uniformly, there were no significant differences between the Feridex-labeled BMSCs group and the non-Feridex-labeled BMSCs group in view of histopathological examination and serological examination (including ALT, AST, Fe3+ levels) at all time points.
The liver function in the model of chemically-induced acutely-injured liver may be repaired by BMSCs implantation. Traced by MRI, BMSCs in the injured liver of rats disperse at a higher rate than in the normally fed ones.
研究经菲立磁标记的同种异体大鼠骨髓干细胞(BMSCs)在化学诱导的急性肝损伤中的定位、迁移情况及其对损伤肝功能的修复作用。
用四氯化碳建立大鼠化学诱导急性肝损伤模型,将经菲立磁标记的BMSCs注入损伤肝脏。对大鼠肝脏进行磁共振成像(MRI)检查,检测注射前6小时以及注射后6小时、1周和5周血清及肝组织中谷丙转氨酶(ALT)、谷草转氨酶(AST)和铁离子(Fe3+)的水平。
模型肝脏可见细胞坏死、肝血窦充血及炎症细胞浸润。普鲁士蓝染色显示90%以上细胞为菲立磁标记的BMSCs阳性,电镜下可见细胞内有铁颗粒。SE-T2WI序列MRI检查显示,注射菲立磁标记的BMSCs后6小时肝脏信号明显减低,注射后1周和5周信号改变部位逐渐扩大。相比之下,损伤肝脏各时间点低信号图像的变化分别比各时间点对照组更明显。同时,肝脏病理损伤减轻,血清中ALT和AST水平下降:菲立磁标记的BMSCs组这些变化比未标记组更明显。各时间点菲立磁标记的BMSCs组与未标记组在组织病理学检查和血清学检查(包括ALT、AST、Fe3+水平)方面均无显著差异。
化学诱导急性肝损伤模型的肝功能可通过植入BMSCs得到修复。通过MRI追踪发现,大鼠损伤肝脏中的BMSCs比正常喂养大鼠中的BMSCs分散速率更高。