人脐血间充质干细胞移植改善肝硬化大鼠的肝功能  

Human umbilical cord blood mesenchymal stem cell transplantation improves the liver function of liver cirrhosis rats

作　　者：廖金卯[1] 胡小宣[1] 李灼日[2] 

机构地区：[1]湖南省人民医院肝病内科,湖南省长沙市410006 [2]海南省人民医院肝胆外科,海南省海口市570311

出　　处：《中国组织工程研究》2013年第27期5005-5011,共7页Chinese Journal of Tissue Engineering Research

摘　　要：背景: 人脐血间充质干细胞移植治疗肝硬化的可行性及机制有待深入探讨。目的: 观察经门静脉移植人脐血间充质干细胞对肝硬化大鼠肝功能及组织病理学改变的影响。方法: 采用四氯化碳法制备肝硬化大鼠模型,造模成功后,细胞移植组经门静脉注射1mLBrdU标记的人脐血间充质干细胞(5×106个),模型组注射等体积的PBS;以经门静脉移植1mL人脐血间充质干细胞的正常大鼠作为对照。细胞移植后4周,取大鼠尾静脉血及肝脏组织进行检测。结果与结论: 细胞移植后4周,与模型组比较,细胞移植组大鼠血清谷丙转氨酶、谷草转氨酶、总胆红素明显降低,而白蛋白明显升高(P<0.01);肝细胞炎性坏死、脂肪变及肝纤维化程度明显改善(P<0.05或P<0.01)。免疫组化及免疫荧光染色显示细胞移植组和对照组大鼠肝组织中均有人脐血间充质干细胞的定植,但细胞移植组BrdU阳性细胞数目明显多于对照组。RT-PCR检测结果显示,细胞移植组大鼠肝组织表达人源性细胞角蛋白18和白蛋白mRNA,而模型组未见。可见人脐血间充质干细胞移植可在一定程度上改善肝硬化大鼠的肝功能及病理损伤,其机制可能与移植细胞在肝硬化大鼠肝内归巢定植并向肝样细胞分化有关。METHODS： Carbon tetrachloride was used to prepare rat model of liver cirrhosis. After the success of modeling, the rats in the cell transplantation group received portal vein injection of 1 mL 5-bromo-2-deoxyuridine -labeled human umbilical cord blood mesenchymal stem cells （5x106）, the model group was injected with the same volume of PBS; the normal rats received 1 mL human umbilical cord blood mesenchymal stem cell transplantation via the portal vein were as the control group. At 4 weeks after transplantation, the rat tail vein blood and liver tissue were obtained for testing. RESULTS AND CONCLUSION： At 4 weeks after cell transplantation, compared with the model group, levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin in the cell transplantation group were significantly decreased, while the albumin level was increased significantly （P 〈 0.01）; the liver cell inflammatory necrosis, steatosis and liver fibrosis were improved significantly （P 〈 0.05 or P 〈 0.01 ）. Immunohistochemistry and immunofluorescence staining showed that human umbilical cord blood mesenchymal stem cell colonization could be seen in the rat liver tissues of the cell transplantation group and control group, but the number of 5-bromo-2-deoxyuridine-positive cells in cell transplantation group was significantly larger than that in the control group. Reverse transcription-PCR test result showed that the expressions of cytokeratin 18 and albumin mRNA could be observed in the rat liver tissue of the cell transplantation group, but no expression could be seen in the control group. It is visible that human umbilical cord mesenchymal stem cells can improve liverfunction and pathological damage of liver cirrhosis rats in a certain extent, which may relate with the intrahepatic homing colonization and hepatocyte-iike cell differentiation of the transplanted cells in the liver cirrhosis rats.

关 键 词：干细胞 干细胞移植 肝硬化 脐血间充质 干细胞移植 定植 归巢 分化 血清白蛋白 纤维化 肝功能 干细胞图片文章 

分 类 号：R394.2[医药卫生—医学遗传学]