同基因与异基因胚胎肝干细胞移植治疗小鼠肝硬化

背景：胚胎肝干细胞移植免疫相关研究较少，同基因与异基因胚胎肝干细胞移植对小鼠肝硬化的治疗作用，目前尚不清楚。目的：观察同种同基因与同种异基因胚胎肝干细胞移植对小鼠肝硬化的治疗作用，以及治疗过程中免疫排斥反应发生情况。方法：采用Ⅳ型胶原酶消化法分离纯化BALB／c与C57BL／6胚胎肝干细胞。104只健康BALB／c小鼠随机分为4组：正常对照组不予任何处理；肝硬化组、同种同基因移植组、同种异基因移植组腹腔注射四氯化碳石蜡油溶液复制肝硬化模型，16周后分别经其尾静脉注射生理盐水，等量同种同基因胚胎肝干细胞和同种异基因胚胎肝干细胞。在移植4周后比较各组受体小鼠存活情况、肝功能恢复情况、肝纤维化程度、免疫细胞（CD4’T、CD8’T、NK、NKT）数目及比值、肝脏病理学变化。结果与结论：同种同基因移植组和同种异基因移植组生存率均为100％，与肝硬化组小鼠存活率67％相比差异有显著性意义（P〈0．05）；各组肝功能和肝纤维化指标差异无显著性意义（P〉0．05）。各组免疫学指标比较差异无显著性意义（户〉0．05）。肝脏组织病理学显示肝组织修复：同种异基因移植组〉同种同基因移植组〉肝硬化组。因此，经尾静脉移植胚胎肝干细胞能提高肝硬化小鼠的生存率、减轻肝细胞坏死程度；同种同基因与同种异基因胚胎肝干细胞移植未发现免疫排斥，对小鼠肝硬化有一定的治疗作用。

Syngeneic and allogeneic fetal liver stem cell transplantation in the treatment of mouse hepatic cirrhosis

BACKGROUND： Immunity of fetal liver stem cell transplantation is rarely reported liver stem cell transplantation in the treatment of hepatic cirrhosis is still unclear. OBJECTIVE： To observe the therapeutic effects of syngeneic and allogeneic fetal on hepatic cirrhosis as well as immune rejections during the therapeutic process. syngeneic and allogeneic fetal iver stem cell transplantation METHODS： The fetal liver stem/progenitor cells from BALB/c and C57BL/6 mice were isolated and purified by the type IV collagen enzyme digestion method. A total of 104 healthy BALB/c mice were randomly assigned to four groups. Normal control group： no treatment; Hepatic cirrhosis group, syngeneic transplantation group and allogeneic transplantation group： 16 weeks after hepatic cirrhosis models of mice were developed by intraperitoneal injection with carbon tetrachloride, physiological saline, syngeneic fetal liver stem cells andallogeneic fetal liver stem cells Were injected, via the caudal vein. Finally, the survival statuses, liver function, hepatic fibrosis index, the number and ratio of immune cells （CD4~T, CD8＊T, NK, NKT） and histopathologic examinations were compared in each group after transplantation 4 weeks. RESULTS AND CONCLUSION： The survival rates in the two transplantation groups were both 100%, which was significantly higher than that in the hepatic cirrhosis group （67%, P 〈 0.05）. The liver function and liver fibrosis index in each group did not show statistical differences （P 〉 0.05）. Immunological tests showed no difference between groups （P 〉 0.05）. Pathohistology examination of hepatic tissue repair： AIIogeneic transplantation group 〉 syngeneic transplantation group 〉 hepatic cirrhosis group. Hence, fetal liver stem cell transplantation via the caudal vein could elevate the survival rate of hepatic cirrhosis mice, alleviate the degree of hepatocyte necrosis. There is no immunologic rejection during syngeneic and all0geneic fetal liver stem cell transplantation that could help to treat hepatic cirrhosis in mice.