骨髓间充质干细胞移植在肝纤维化治疗中的应用  

Bone marrow mesenchymal stem cells as therapy for hepatic fibrosis

作　　者：吕素莉[1] 马勇[2] 丁体龙[2] 

机构地区：[1]蚌埠医学院医学检验系,安徽蚌埠233030 [2]解放军第123医院南京军区肝病中心,安徽蚌埠233015

出　　处：《临床肝胆病杂志》2012年第11期819-823,共5页Journal of Clinical Hepatology

基　　金：南京军区医学科技创新经费资助重点课题(11Z012)

摘　　要：目的探讨大鼠骨髓间充质干细胞(BMSC)对肝纤维化大鼠模型的治疗效果,为临床自体BMSC移植治疗肝脏疾病提供实验基础和理论依据。方法四氯化碳(CCl4)腹腔注射构建SD大鼠肝纤维化模型。以绿色荧光蛋白(GFP)标记的正常SD大鼠BMSC为细胞来源,于造模后第10周经尾静脉植入模型鼠体内,对照组同法注入生理盐水。4周后取大鼠肝脏进行病理学检测,同时采集大鼠血液,检测血清肝纤维化指标和肝功能指标。结果 (1)成功构建SD大鼠肝纤维化模型。(2)体外分离获得了高纯度贴壁生长的大鼠BMSC,并用携带GFP报告基因的慢病毒成功对其进行感染,感染率达80%以上。(3)经BMSC移植的大鼠肝脏中可检测到GFP阳性的细胞,主要沿着中央静脉及汇管区周围纤维间隔分布。免疫组织化学结果显示GFP阳性细胞呈肝样细胞形态,且与肝组织相容。(4)BMSC移植组与模型对照组和生理盐水组相比,病理检测肝纤维化程度减轻,血清学指标好转。结论BMSC移植能抑制大鼠肝纤维化发展,部分逆转肝纤维化进程,有效改善肝脏功能,为临床自体BMSC移植治疗肝脏疾病提供实验基础。Objective To investigate the therapeutic effect of rat bone marrow mesenchymal stem cells（BMSC） in a rat model of liver fibrosis,so as to provide an experimental foundation and theoretical basis for the clinical treatment of human hepatic disease by transplantation of autologous BMSC.Methods Carbon tetrachloride（CCl4） was injected intraperitoneally to induce rat liver fibrosis.BMSC were harvested from uninduced,healthy rats,infected with lentivirus expressing green fluorescent protein（GFP）,and transplanted into the fibrosis-induced rat via tail vein injection at week 10 after model establishment.A negative control group was injected with saline.Four weeks later,the livers were excised for pathologic examination and the venous blood was collected to test the serological fibrosis parameters and indices of liver function.Results The rat model of liver fibrosis was successfully established.More than 80% of the isolated BMSC were successfully infected with the GFP lentiviral vector.After transplantation,GFP-positive cells were detected in the livers of recipient rats,with the majority being distributed along the fibrous septa around the central vein and portal area.In addition,the GFP-positive cells showed a hepatocyte-like structure and were compatible with hepatic tissue.The rats treated with BMSC had appreciably less hepatic fibrosis and better serological indices than the untreated model group.Conclusion BMSC transplantation can inhibit the progression of liver fibrosis and possibly restore liver function in a rat model.

关 键 词：肝硬化 干细胞移植 骨髓细胞 间质干细胞 

分 类 号：R575.2[医药卫生—消化系统]