单倍体相合细胞移植诱发小鼠移植物抗肿瘤效应的分析  

Analysis on graft versus tumor effect induced by haploidentical transplantation in mice

作　　者：林浩[1] 叶韵斌[1] 李晓峰[1,2] 陈强[1] 

机构地区：[1]福建省肿瘤医院肿瘤免疫学研究室,福建省福州市350014 [2]福建省泉州市中医院肿瘤科,福建省泉州市362000

出　　处：《中国组织工程研究与临床康复》2008年第3期456-460,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：福建省科技厅重点科技项目(2006Y0011);福建省自然基金资助项目(C0310035);福建省医学创新课题(2003-CX-16)~~

摘　　要：目的:异基因造血干细胞移植是治疗恶性肿瘤的一种有效方法,但在异基因造血干细胞移植时,如何在减轻移植物抗宿主病的同时保留并加强移植物抗肿瘤效应是目前临床面临的一大课题。观察输注经与未经60Co照射的单倍体相合细胞治疗CB6F1小鼠肝癌模型中移植物抗宿主病临床表现,探讨输注经照射单倍体相合细胞在治疗实体瘤中减轻移植物抗宿主病的作用。方法:实验于2006-03/2007-03在福建省肿瘤医院肿瘤免疫学研究室和福建省疾病预防控制中心动物房完成。①实验材料:来源于BABL/C小鼠的肝癌H22细胞株由武汉大学中国典型培养物保藏中心提供。SPF近交系小鼠由北京维通利华实验动物技术有限公司提供。实验过程中对动物处置符合动物伦理学标准。②实验方法:以皮下接种肝癌细胞(H22)的CB6F1(BABL/C×C57BL/6杂交鼠,简称F1)雌性小鼠为受体鼠,经环磷酰胺腹腔化疗后,取C57BL/6小鼠的新鲜骨髓及脾脏细胞作为供体细胞,供体细胞分为经60Co照射和未经60Co照射。将F1小鼠随机分为3组:单纯化疗组、化疗+未经60Co照射细胞组、化疗+经60Co照射细胞组。观察3组小鼠移植物抗宿主病表现,并给予临床评分。③实验评估:于移植后第17天取小鼠皮肤、肠、肝、脾组织制备病理切片,观察移植物抗宿主病病理学改变所反应的情况,并检测小鼠瘤重和抑瘤率。结果:①化疗+经60Co照射细胞组小鼠移植物抗宿主病的临床表现明显轻于化疗+未经60Co照射细胞组(P<0.05)。②化疗+经60Co照射细胞组小鼠的皮肤、肠、肝、脾组织移植物抗宿主病的细胞病理学改变轻于化疗+未经60Co照射细胞组。③单纯化疗组与化疗+未经60Co照射细胞组、化疗+经60Co照射细胞组瘤重比较差异显著[(1.34±0.45)g,(0.6±0.38)g,(0.28±0.15)g,P<0.05]。化疗+未经60Co照射细胞组抑瘤率为55.22%,化疗+经60Co照射细胞组抑瘤率为79.22%。�AIM： Allogeneic hematopoietic stem cell transplantation is a efficient way to cure malignancies, but how to remaining and strengthen graft-versus-tumor effect when reduce graft-versus-host disease in the course of allogeneic hematopoietic stem cell transplantation is a big topic for present clinic. This test proves into the role of infusion of haploidentical cells radiated with ^60Co in the cure of solid tumors to ease the graft-versus-host disease through observing the clinical features of graft-versus-host disease in the cure of hepatoma cells （H22） of Fl mice by infusion of haploidentical cells respectively with and without radiation of ^60Co among groups. METHODS： Experiments were conducted at the Department of Tumor Immunology of Fujian Tumor Hospital and Fujian Center for Disease Control and Prevention from March 2006 to March 2007. （1）Hepatoma cells （H22） from BABL/C mice were provided by China Center for Type Culture Collection of Wuhan University. SPF inbred line mice were offered by Beijing Vital River Company. Animal intervention met the animal ethical standard. （2）Female CB6F1 mice （F1 mice in short） which had been hypodermically inoculated with hepatoma cells （H22） were as recipients, and the C57BL/6 mice were as the donors. CB6F1 mice received intraperitoneal chemotherapy with cyclophosphamide. Fresh bone marrow and spleen cells from C57BL/6 mice were as donor cells, which were divided into with or without radiation of ^60Co. Fl mice were randomly assigned into a simple chemotherapy group, a chemotherapy plus non-^60Co irradiated group and a chemotherapy plus ^60Co irradiated group. The characteristics of graft-versus-host disease were observed, and the clinical grades were determined. （3） Pathological changes in the skin, intestines, liver and spleen of mice were detected after transplantation at day 17. The pathological grades of graft-versus-host disease were determined. The weight of the tumor and the anti-tumor rate of different groups were inspected. RESULTS：

关 键 词：单倍体相合移植 移植抗宿主病 移植物抗肿瘤 NST 

分 类 号：R730.26[医药卫生—肿瘤]