中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (14): 2530-2534.doi: 10.3969/j.issn.1673-8225.2011.14.014

• 干细胞因子及调控因子 stem cell factors and regulatory factors • 上一篇    下一篇

粒细胞集落刺激因子对骨髓极小胚胎样干细胞的动员和募集

郭慧娟1,王  健1,张兴秀1,郑  敏2   

  1. 1重庆医科大学附属第二医院神经内科,重庆市  400010
    2重庆医科大学基础医学院组胚教研室,重庆市  400016
  • 收稿日期:2010-11-17 修回日期:2011-01-23 出版日期:2011-04-02 发布日期:2013-11-02
  • 通讯作者: 郑敏,副教授,硕士生导师,重庆医科大学基础医学院组胚教研室,重庆市 400016 zmdwj625@gmail.com
  • 作者简介:郭慧娟★,女,1983年生,山东省济南市人,汉族,重庆医科大学在读硕士,主要从事神经病学方面的研究。 guohuijia88@163.com
  • 基金资助:

    重庆市自然科学基金(2010BB5096),重庆市卫生局科研课题(2009-2-207)。

Effect of granulocyte-colony stimulating factor on mobilization and recruitment of very small embryonic-like stem cells

Guo Hui-juan1, Wang Jian1, Zhang Xing-xiu1, Zheng Min2   

  1. 1Department of Neurology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing  400010, China
    2Department of Basic Medical Sciences, Chongqing Medical University, Chongqing  400016, China
  • Received:2010-11-17 Revised:2011-01-23 Online:2011-04-02 Published:2013-11-02
  • Contact: Zheng Min, Associate professor, Master’s supervisor, Department of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China zmdwj625@gmail.com
  • About author:Guo Hui-juan★, Studying for master’s degree, Department of Neurology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China guohuijia88@163.com
  • Supported by:

    the Natural Science Foundation of Chongqing, No. 2010BB5096*; the Science and Technology Subject of Health Bureau of Chongqing, No. 2009-2-207*

摘要:

背景:极小胚胎样干细胞(very small embryonic-like stem cells,VSEL-SCs)是一种非造血干细胞,具有类似胚胎干细胞的生物学特性。目前,心肌梗死后VSEL-SCs的研究较多,而急性脑梗死后VSEL-SCs的动员及其修复受损组织的研究在国内外报道尚少。
目的:观察小鼠急性脑梗死后粒细胞集落刺激因子对骨髓来源的VSEL-SCs动员、募集及其作用机制。
方法:线栓法制备小鼠大脑中动脉栓塞模型,腹腔内分别注射粒细胞集落刺激因子和生理盐水,观察术后神经功能评分,流式细胞分析计数动员到外周血中的VSEL-SCs数量;ELISA方法分析术后血浆及缺血侧脑组织中基质细胞衍生因子1水平的动态变化,免疫组化观察缺血边缘带的基质细胞衍生因子1阳性细胞表达。
结果与结论:与生理盐水组相比,术后108 h粒细胞集落刺激因子组造模后神经功能评分明显降低(P < 0.05);术后72,108 h粒细胞集落刺激因子组动员到外周血的VSEL-SCs含量高于生理盐水组( < 0.05);粒细胞集落刺激因子组血浆和脑组织中基质细胞衍生因子1水平高于生理盐水组(P < 0.05),血浆基质细胞衍生因子1水平与动员到外周血的VSEL-SCs数量成正相关;脑组织免疫组化中,粒细胞集落刺激因子组基质细胞衍生因子1阳性细胞多于生理盐水组。结果显示粒细胞集落刺激因子能使更多的VSEL-SCs从骨髓动员到外周血中,粒细胞集落刺激因子对缺血脑组织的保护作用,可能在于其能够使缺血边缘带的基质细胞衍生因子1表达增加,并通过CXCR4/SDF-1轴的趋化作用,使募集到梗死区域的CXCR4+细胞增多来实现的。

关键词: 极小胚胎样干细胞, 骨髓干细胞, 神经干细胞, 动员, 脑梗死, 脑修复, 小鼠

Abstract:

BACKGROUND: A population of very small embryonic-like stem cells (VSEL-SCs) is a kind of non-hemopoietic stem cells, which has similar biological characteristics to embryonic stem cells. Currently, most studies concerning VSEL-SCs after myocardial infarction, but mobilization of VSEL-SCs and its effect on repair damaged tissues after acute cerebral infarction remain poorly understood. 
OBJECTIVE: To investigate the effects of granulocyte-colony stimulating factor (G-CSF) on mobilization of bone marrow-derived VSEL-SCs, recruitment and mechanism after mouse acute cerebral infarction.
METHODS: Mouse middle cerebral artery occlusion (MCAO) model was induced by using the filament occlusion method. G-CSF and normal saline were separately injected to MCAO model. Neurological scales were evaluated. The number of VSEL-SCs mobilized into peripheral blood was checked by fluorescence-activated cell sorting analysis. The level of stromal cell derived factor-1 (SDF-1) in plasma and cerebral tissue were determined by ELISA assay. Positive expression of SDF-1 in ischemic regions was detected by immunohistochemistry.
RESULTS AND CONCLUSION: Compared with the normal saline group, the neurological behavioral scale of G-CSF treated group was significantly lower at 108 hours after operation ( < 0.05). G-CSF groups mobilized more VSEL-SCs into peripheral blood compared with the operated control group at 72 and 108 hours ( < 0.05). The SDF-1 density significantly increased in the plasma and brain tissues of the G-CSF group than that of the normal saline group (P < 0.05), and positive correlation can be seen between the number of VSEL-SCs mobilized into peripheral blood and the SDF-1 plasma concentration. The positive expression of SDF-1 in the G-CSF group was greater than that of the normal saline group. The results indicated that G-CSF mobilized VSEL-SCs in adult MCAO mouse bone marrow into peripheral blood. The mechanism of beneficial effects of G-CSF possibly related to increase of SDF-1 expression in the infracted tissues and recruitment of more VSEL-SCs through CXCR4/SDF-1 axis.

中图分类号: