CXCR4基因修饰骨髓间充质干细胞对照射损伤小鼠造血重建的影响  

Influence of CXCR4 Overexpressed Mesenchymal Stem Cells on Hematopoietic Recovery of Irradiated Mice

作　　者：臧宇[1] 陈伟[1] 徐开林[1] 潘彬[1] 曾令宇[1] 

机构地区：[1]徐州医学院附属医院血液科,江苏徐州221002

出　　处：《中国实验血液学杂志》2013年第5期1261-1265,共5页Journal of Experimental Hematology

摘　　要：本研究旨在探讨过表达CXCR4基因的骨髓间充质干细胞(mesenchymal stem cells,MSC)移植对照射损伤小鼠造血重建的影响。采用293FT细胞包装共表达EGFP和Cxcr4慢病毒载体,转导MSC建立稳定共表达EGFP和CXCR4基因MSC(CXCR4-MSC),同时建立稳定表达EGFP的MSC(EGFP-MSC)作为对照,经尾静脉输注接受亚致死剂量(总剂量3.5 Gy)照射的BALB/c小鼠。MSC的输注量5×105,设立单纯照射组为单纯对照组。观察小鼠的一般生存状态,统计小鼠生存率。分别于第3、7、14、21、28 d外周血计数白细胞(WBC)和红细胞(RBC),流式细胞术(FCM)检测网织红细胞与网织血小板比例及血小板(Plt)数量。病理观察移植后各组骨髓、脾脏恢复情况。PCR检测MSC在受鼠体内植入情况。结果表明,各组小鼠移植后血象呈先下降、继而上升的一般趋势,其中WBC在1周后开始恢复,且CXCR4-MSC组恢复速度明显快于其他两组,差异具有统计学意义(P<0.05)。病理结果显示,CXCR4-MSC组造血器官照射损伤后修复较快。PCR检测发现,移植后7、14、21、28 d均可在受亚致死剂量照射的受鼠体内检测到供体MSC。结论:输注过表达CXCR4基因的MSC可增加MSC植入,并促进照射损伤小鼠造血功能的恢复。This study was aimed to investigate the homing capacity of CXCR4 overexpressed mesenchymal stem cells （MSC） and their effect on hematopoietic recovery. The 293FT packaging cell line was transfected with the recombinant lentiviral vector LV-CXCR4-IRES-EGFP and LV-IRES-EGFP to produce lentivirus. Mouse MSC were then infected with viral supernatant. Male BALB/c mice were sublethally irradiated and then were injected intravenously with 5 × 105 MSC. General status and survival rate of mice were observed every day. On day 3,7,14,21 and 28, peripheral blood samples were collected to calculate the number of white blood cells （WBC） and red blood cells （RBC） , the ratio of reticulocyte to platelet, the number of platelet was detected by flow cytometry. The recovery of bone marrow and spleen was pathologically monitored. The proportion of MSC implantation was analysed by PCR. The results showed that the peripheral blood cells displayed the tendency of firstly increasing and then decreasing to their normal level. Generally, recovery of WBC level was earlier in mice infused with MSC （ P 〈 0.05 ）. The histopathological examination of spleen and bone marrow showed a faster hematopoietic recovery in CXCR4-MSC group than the other two groups. And the donor MSC could be detected in the recipients on day 7,14,21 and 28. It is concluded that infusion of CXCR4-MSC enhances the implantation of hematopoietic stem cells and promotes hematopoietic recovery of the sublethally irradiated mice.

关 键 词：CXCR4 间充质干细胞 造血重建 照射损伤 

分 类 号：R457.7[医药卫生—治疗学] R818[医药卫生—临床医学]