基础医学与临床 ›› 2010, Vol. 30 ›› Issue (1): 67-70.

• 研究论文 • 上一篇    下一篇

基质细胞衍生因子受体在造血干/祖细胞宫内移植中的作用

区文超 迟东升 孙德胜 鲁树坤   

  1. 广州中医药大学第二临床学院 北京大学深圳医院超声影像科
  • 收稿日期:2008-09-24 修回日期:2009-04-29 出版日期:2010-01-05 发布日期:2010-01-05
  • 通讯作者: 区文超

Role of stroma cell-derived factor-1 receptor in utero transplantation

Wen-chao OU, Dong-sheng CHI, De-sheng SUN, Shu-kun LU   

  1. the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Shenzheng Hospital, Peking University
  • Received:2008-09-24 Revised:2009-04-29 Online:2010-01-05 Published:2010-01-05
  • Contact: Wen-chao OU,

摘要: 目的 探讨基质细胞衍生因子受体(CXCR4)在造血干/祖细胞(HSC)宫内移植归巢中的作用。方法 分离人脐血CD34+细胞,用流式细胞仪检测SCF、IL-6处理前后细胞表面CXCR4(CD184)的表达及在Transwell板中的迁移率。在BALB/c胎鼠孕13~14d期间经胎鼠腹腔注射分别经不同处理的CD34+细胞,胎鼠出生1个月后取骨髓用流式细胞仪检测人CD45细胞。结果 预处理后表达CD184的CD34+细胞的百分数分别由原来的9.58% 1.56%上升为 19.32% 3.64%。CD34+/CXCR4+high细胞迁移率显著增高,但迁移作用可以被antiCXCR4mAb和PTX明显抑制。SCF和IL-6预处理组胎鼠人CD45细胞阳性率显著高于其他组。抗CXCR4抗体或PTX预处理组人CD45细胞检出率显著降低。结论 增加CD34+细胞CXCR4的表达有助于宫内移植HSC的归巢,HSC宫内移植归巢过程依赖CXCR4受体,SDF-1/CXCR4调节信号通过Gi蛋白进行跨膜传导。

Abstract: Objective To explore the effect of stroma cell-derived factor receptor CXCR4 on the homing of the hematopoietic stem/progenitor cells in utero transplantation. Methods CD34+ cells were separated by Ficoll density gradient centrifugation and MiniMACS and stimulated for 48h by SCF、IL-6 cytokines prior to transplantation. The changes of the CD184(CXCR4) expressions and transmigrate rates of the CD34+ cells were analysed by flow cytometer. The 1 105 cells pretreated with different treatment were transplanted into the abdominal cavity of the fetal BALB/c mouse in the pregnant days 13~14. The human CD45 cells as the marker of graft were detected by flow cytometry after 1 month the fetus born. Results Expression changes of CD184 on CD34+ cells were from 9.58% 1.56% to 19.32% 3.64% after SCF and IL-6 stimulation. The CD34+/CXCR4high cells exhibited significant increases in SDF-1 mediated chemotaxis compared with the CD34+/CXCR4low cells. Transmigration of CD34+/CXCR4high was inhibited by pretreatment with antiCXCR4mAb and PTX. The positive rates of human CD45 cells detected in the fetal mouse were significantly higher in the SCF and IL-6 pretreatment group. This effects were significantly abrogated after the addition of antiCXCR4mAb or PTX. Conclusion Up-regulation of CXCR4 expression may be useful for improving hematopoietic stem/progenitor cells homing in utero transplantation. This homing process is mediated and depended on the CXCR4 receptors. The signal transduction is mediated by PTX-sensitive Gi protein.