摘要
背景:自体来源诱导性多能干细胞移植改善肝组织结构与功能是慢性乙型肝炎性肝损伤治疗的新研究方向。目的:观察自体皮肤来源诱导性多能干细胞移植治疗HBV转基因小鼠慢性肝损伤的效果。方法:用腹腔注射四氯化碳建立HBV转基因小鼠(购于北京维通达生物技术有限公司)慢性肝损伤模型;造模开始注射四氯化碳第1周后,将模型小鼠皮肤成纤维细胞体外重编程为诱导性多能干细胞并进行鉴定;造模6周结束后第2天,通过门静脉途径将0.1 mL诱导性多能干细胞移植到模型小鼠肝内,对照组注射0.1 mL PBS;移植后7,14 d,冰冻切片观察诱导性多能干细胞定植情况;ELISA法检测小鼠肝功能;石蜡切片苏木精-伊红染色观察肝组织病理学变化。结果与结论:(1)模型小鼠皮肤成纤维细胞在体外成功重编程为诱导性多能干细胞,具有多向分化潜能;(2)移植后7 d,实验组小鼠肝内可见荧光标记的诱导性多能干细胞;(3)实验组小鼠血清谷丙转氨酶、谷草转氨酶、谷氨酰转肽酶、总胆红素水平低于对照组,白蛋白水平高于对照组(P <0.05);(4)实验组小鼠肝脏中肝细胞变性、坏死及炎细胞浸润较对照组明显改善;(5)结果提示,自体来源诱导性多能干细胞门静脉移植可治疗小鼠慢性乙型肝炎肝损伤。
BACKGROUND:Autologous source induced pluripotent stem cell transplantation to improve liver tissue structure and function is a new research direction in the treatment of liver injury caused by chronic hepatitis B.OBJECTIVE:To observe the effect of autologous skin-derived induced pluripotent stem cell transplantation on chronic hepatic injury in HBV transgenic mice.METHODS:A chronic hepatic injury model of HBV transgenic mice(provided by the Beijing Vitalstar Biotechnology Co.,Ltd.in China)was established with intraperitoneal injection of carbon tetrachloride.At1week after injection of carbon tetrachloride,skin fibroblasts from the model mice were reprogrammed into induced pluripotent stem cells and identified in vitro.Induced pluripotent stem cells(0.1mL)were transplanted into the liver of model mice through the portal vein pathway as experimental group,and PBS(0.1mL)was injected into the other mice as control group.Colonization of induced pluripotent stem cells was observed by frozen section at7and14days of transplantation.Liver function of the mice was detected by ELISA,and liver histopathological changes were observed by hematoxylin-eosin staining of paraffin section.RESULTS AND CONCLUSION:Skin fibroblasts from model mice were successfully reprogrammed into induced pluripotent stem cells in vitro that had multipotent differentiation potential.At7days after transplantation,fluorescent labeled induced pluripotent stem cells were found in the mouse liver of the experimental group.The levels of serum alanine aminotransferase,aspartate aminotransferase,glutamyl transpeptidase,and total bilirubin in the experimental group were lower than those in the control group,and the level of albumin was higher than that in the control group(P<0.05).Liver cell degeneration,necrosis and inflammatory cell infiltration in the mouse liver of the experimental group were significantly improved as compared with the control group.These results suggest that portal vein transplantation of autologous source induced pluripotent stem cells can treat chronic hepatitis B-induced liver injury in mice.
作者
潘丽娟
王荣丽
Pan Lijuan;Wang Rongli(Section of Infection Management, the Affiliated Hospital of Southwest Medical University,Luzhou 646000, Sichuan Province, China)
出处
《中国组织工程研究》
CAS
北大核心
2019年第5期773-778,共6页
Chinese Journal of Tissue Engineering Research
作者简介
潘丽娟,女,1989年生,四川省夹江县人,汉族,2017年西南医科大学毕业,硕士,主要从事感染与感染管理方面的研究;通讯作者:王荣丽,硕士,教授,西南医科大学附属医院感染管理科,四川省泸州市646000
