人脐带间质干细胞对大鼠的免疫毒性研究  

Immune toxicity of human umbilical cord mesenchymal stem cells on rats

作　　者：李岩[1] 刘拥军 秦超[1] 陈威[1] 徐萌 刘广洋 朱德琳 高虹[1] 

机构地区：[1]中国医学科学院医学实验动物研究所,北京100050 [2]和泽生物科技有限公司干细胞研发中心,北京100070

出　　处：《药物不良反应杂志》2011年第2期78-84,共7页Adverse Drug Reactions Journal

基　　金：中国医学科学院国际标准药物安全评价技术平台建设项目(2008ZX09305-001)

摘　　要：目的:研究人脐带间质干细胞(UCMSC)对Wistar大鼠的免疫毒性作用。方法:SPF级Wistar大鼠112只分为4组:溶媒组(给予溶媒5 ml/kg)、低剂量组(给予人UCMSC 1×107个/kg)、高剂量组(给予人UCMSC 5×107个/kg)和对照组(给予大鼠UCMSC 1×107个/kg)。每组28只大鼠,雌雄各14只。大鼠尾静脉注射给药,2周1次,共注射4次。给UCMSC后每周进行受体鼠临床移植物抗宿主病(GVHD)评分,末次注射UCMSC后1、13周检测血IgG、IgM含量,CD3+、CD4+、CD8+T细胞数量,并对大鼠淋巴结、胸腺、脾脏进行脏器系数计算和组织病理学检查。结果:给予UCMSC后,各组大鼠的GVHD评分值均为0。末次给予UCMSC后1周,低、高剂量组雌性大鼠IgG[(0.65±0.12)、(0.63±0.14)g/L]和IgM含量[(0.06±0.01)、(0.06±0.01)g/L]明显高于溶媒组雄性大鼠[(0.41±0.17)g/L、(0.04±0.01)g/L,P<0.01或P<0.05];高剂量组雄性大鼠IgM含量[(0.05±0.01)g/L]明显高于溶媒组雄性大鼠[(0.03±0.01)g/L,P<0.01];对照组雌性、雄性大鼠IgM[(0.06±0.02)、(0.05±0.02)g/L]也明显高于溶媒组(P<0.01或P<0.05)。末次给予UCMSC后13周,各剂量组雌、雄性大鼠IgG、IgM与溶媒组相比差异均无统计学意义(均P>0.05)。末次给予UCMSC后1周,低、高剂量组雌性大鼠的脾脏系数[分别为(0.274±0.016)%、(0.294±0.019)%]明显高于溶媒组[(0.232±0.012)%,P<0.01];高剂量组雄性大鼠的脾脏系数[(0.242±0.027)%]明显高于溶媒组[(0.202±0.012)%,P<0.01];对照组雌、雄性大鼠脾脏系数[分别为(0.261±0.019)%、(0.236±0.014)%]也明显高于溶媒组(P<0.05或P<0.01)。末次给予UCMSC后13周各组大鼠的脾脏和胸腺系数差异均无统计学意义(均P>0.05)。各组大鼠CD3+、CD4+、CD8+T细胞百分比及CD4+/CD8+比值均在正常范围内。各组大鼠胸腺、脾脏和肠系膜淋巴结组织病理学检查均未见明显异常。结论:人脐带间质干细胞可引起正常Wistar大鼠免疫球蛋白含量和脾脏系数的升高,该作用具有一过性�Objective： To investigate the immune toxicity of human umbilical cord mesenchymal stem cells（UCMSC） on Wistar rats.Methods： One hundred and twelve SPF grade Wistar rats were randomly divided into 4 groups： the solvent group（a dose of solvents 5 ml/kg）,the low-dose group（a dose of 1×107 human UCMSC/kg）,the high-dose group（a dose of 5×107 human UCMSC/kg） and the control group（a dose of 1×107 rat UCMSC/kg）.Each group comprised 28 rats（14 males and 14 females）.UCMSC once every 2 weeks was given via the caudal vein for 4 doses.The graft versus host diseases（GVHD） scores were evaluated every week after the UCMSC injection start.The IgG and IgM levels and the numbers of T cell subtypes（CD3＋,CD4＋,and CD8＋） were measured.The pathological changes in lymphonode,thymus and spleen were observed and organ coefficients were calculated 1 and 13 weeks after the final dose of UCMSC.Results： The GVHD scores were 0 after injection of UCMSC in all groups.One week after the final dose of UCMSC,the IgG and IgM levels of female rats in the low-dose group[（0.65±0.12） and（0.63±0.14）g/L,respectively]and the high-dose group[（0.06±0.01） and（0.06±0.01） g/L,respectively] increased markedly than those in the solvent group [（0.41±0.17） g/L and（0.04±0.01） g/L,P0.05 and P0.01,respectively].Thirteen weeks after the final dose of UCMSC,the IgM level of the male rats in the high-dose group [（0.05±0.01） g/L] increased markedly than that in the solvent group [（0.03±0.01） g/L,P0.05].The IgM levels of male and female rats in the control group [（0.06±0.02） and（0.05±0.02） g/L,respectively]increased markedly than those in the solvent group [（0.05±0.02） g/L,both P0.05].There were no statistically differences in the IgG and IgM levels of male and female rats among groups 13 weeks after the final dose of UCMSC（all P0.05）.One week after the final dose of UCMSC,the spleen coefficient of female rats in the low-dose group[（0.274±0.016） %] and the high-d

关 键 词：脐带间质干细胞 免疫毒性 大鼠 Wistar 

分 类 号：R392[医药卫生—免疫学]