BMMSC输注对脐血CIK／NK细胞在荷瘤小鼠体内抗肿瘤效应的影响  

Influences of bone nmrrow mesenchymal stem cells infusion on anti-tumor activities of cytokine-induced killer/natural killer cells from umbilical cord blood in K562 NOD/SCID mice

作　　者：黎阳[1] 王潇娉[1] 吴燕峰[1] 黄文革[1] 黄科[1] 黄绍良[1] 魏菁[1] 周敦华[1] 方建培[1] 薛红漫[1] 

机构地区：[1]中山大学孙逸仙纪念医院儿科,广州510120

出　　处：《中华器官移植杂志》2011年第9期553-557,共5页Chinese Journal of Organ Transplantation

基　　金：基金项目：国家自然科学基金（30500469）;广东省科技计划项目（200813030301066,201013080701074）;广州科学仪器协作共用网基金（2006034）

摘　　要：目的利用荷瘤小鼠来探讨不同的输注途径以及不同时间输注骨髓间充质干细胞（BMMSC）对脐血来源细胞因子诱导的杀伤（CIK）／自然杀伤（NK）细胞在体内抗肿瘤效应的影响。方法NOD／SCID小鼠共56只，分为7组，每组小鼠经尾静脉输注K562细胞后12h分别进行以下实验：同时经尾静脉输注人BMMSC＋CIK／NK细胞（A组）；经尾静脉相隔48h分别输注人BMMSC和CIK／NK细胞（B组）；经小鼠胫骨骨髓腔输注人BMMSC，同时经尾静脉输注CIK／NK细胞（C组）；经小鼠胫骨骨髓腔输注人BMMSC，48h后经尾静脉输注C1K／NK细胞；经小鼠胫骨骨髓腔输注人BMMSC，48h后经尾静脉输注CIK／NK细胞（E组）：较其他组延迟48h经尾静脉输注CIK／NK细胞（F组）；除输注K562细胞外，不输注其他细胞（G组）。计算各组小鼠的生存曲线，检N4,鼠外周血、骨髓、肝、脾和肺等脏器的肿瘤细胞负荷情况。结果A、B、G组小鼠的存活时间短于C、D、E、F组（P〈O．05）；A、B、G组间以及C、D、E、F组间小鼠的存活时间的差异均无统计学意义（P〉O．05）；A、B、G组小鼠外周血、骨髓涂片中肿瘤细胞的比例高于C、D、E、F组（P〈0．05）。A、B、G组小鼠外周血、骨髓及肝、脾、肺组织匀浆中人肿瘤细胞标记CD33的表达率高于C、D、E、F组（P〈O．05）；A、G组小鼠肝、脾、肺组织匀浆中CD33表达率高于B组（P〈O．05）；C组小鼠肺组织匀浆中CD33表达率高于D组（P〈O．05）。结论同部位注射BMMSC可明显抑制CIK／NK细胞在荷瘤小鼠体内的抗肿瘤作用，而分部位注射，则BMMSC的抑制作用明显减弱。提前输入的BMMSC在体内仍会削弱CIK／NK细胞的抗肿瘤作用。Objective To explore the influences of bone marrow mesenchymal stem cells （BMMSC） infused via different ways and at different time points on anti-tumor activities of cytokine- induced killer （CIK）/natural killer （NK） cells from umbilical cord blood in K562 NOD/SCID mice. Methods Fifty-six NOD/SCID mice were divided into 7 groups. The following experiments were carried out at 12th h after K562 cells were infused. Group A： BMMSC （intravenous injection, i. v. ） ＋ CIK/NK cells （i. v. ,at the same time） ; Group B： BMMSC （i. v. ） ＋ CIK/NK cells （i. v. ,48 h after BMMSC infusion） ; Group C： BMMSC （cavitas medullaris） ＋ CIK/NK cells （i. v. ,at the same time） ; Group D： BMMSC （cavitas medullaris） ＋ CIK/NK cells （i. v. ,48 h after BMMSC infusion） ; Group E.. CIK/NK cells （i. v. ） ; Group F.. CIK/NK cells （i. v. ,50 h after K562 cells inoculation） ; Group G （control group） .. No other cells were infused in addition to K562 cells. The survival curve of NOD/ SC1D mice in each group was drawn, and the tumor cell load of the peripheral blood, bone marrow, liver,spleen and lung was detected by using morphology, flow cytometry and histological methods. Results The average survival time of groups A,B,G was significantly shorter than that of groups C, D, E, F （P〈0. 05）. There was no significant difference in average survival time among groups A, B and G and that between groups C, D, E and F （P〉0. 05）. The ratio of tumor cells on peripheral blood and bone marrow smears in groups A, B and G was higher than that in groups C, D, E and F. The expression of human CD33 as the tumor marker in peripheral blood, bone marrow and liver, spleen, lung tissue homogenates of groups A, B and G was higher than that of group C, D, E and F （P〈 0. 05）. Whereas, the expression of CD33 in the liver, spleen, lung tissue homogenate of groups A and G was significantly higher than that of group 13. The expression of CD33 in the lung tissue homogenate of group C was sign

关 键 词：NOD/SCID小鼠 骨髓 间质干细胞移植 脐血 杀伤细胞 淋巴因子激活 抗肿瘤效应 

分 类 号：R73-3[医药卫生—肿瘤]