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Inoculation of murine bone marrow mesenchymal stem cells induces tumor necrosis in mouse with orthotopic hepatocellular carcinoma
Author(s): 
Pages: 453-458
Year: Issue:  5
Journal: JOURNAL OF PEKING UNIVERSITY(HEALTH SCIENCES)

Keyword:  肝肿瘤实验性间质干细胞模型动物细胞分化小鼠;
Abstract: 目的:观察小鼠骨髓间充质干细胞(mesenehymal stem cells,MSCs)移植对H22原位肝癌移植小鼠生存期的影响,探讨小鼠骨髓MSCs在肝癌微环境中是否向肝细胞分化和可能的抗肿瘤机制.方法:体外利用贴壁培养法联合免疫磁珠阴性分选CD45-、CD11b-细胞法制备BALB/c小鼠骨髓MSCs,流式细胞仪行细胞表面标志鉴定,采用绿色荧光染料羧基荧光素二醋酸盐琥珀酰亚胺酯[5(6)-carboxyfluoresce indiacetate N-succinimidyl ester,CFSE]对其标记后备用.随机取12只8周龄BALB/c小鼠,肝脏原位注射法建立小鼠H22原位肝癌移植模型,建模1周后随机分为MSCs移植组和对照组,开腹亢视下分别注射入肝癌组织和/或同一肝叶的正常肝组织内.观察荷瘤小鼠生存期,利用免疫荧光法和激光共聚焦技术检测小鼠肝组织白蛋白表达,并行常规组织学检查.结果:MSCs移植组平均生存期为25 d(95%可信区间:22~28 d),对照组平均生存期为21 d(95%可信区间:20~23 d),但组间生存期差异无统计学意义(P=0.0713).激光共聚焦显微镜观察到在肿瘤边缘和瘤体内可见CFSE标记细胞有白蛋白表达;另与对照组相比,MSCs移植组肝癌组织内出现大片坏死.结论:小鼠骨髓MSCs可在原位肝癌移植小鼠模型的肝脏定植,并且能分化为具有肝细胞功能的肝细胞样细胞,同时可能诱发肿瘤细胞坏死,机制有待进一步研究.
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