Progenitor Cell Mobilization and Recruitment: SDF-1, CXCR4, α4-integrin, and c-kit

被引:57
作者
Cheng, Min [1 ]
Qin, Gangjian [2 ]
机构
[1] Huazhong Univ Sci & Technol, Dept Cardiol, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
[2] Northwestern Univ, Feinberg Cardiovasc Res Inst, Dept Med Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA
来源
GENETICS OF STEM CELLS, PT A | 2012年 / 111卷
关键词
COLONY-STIMULATING FACTOR; ACUTE MYOCARDIAL-INFARCTION; CHEMOKINE RECEPTOR CXCR4; HEMATOPOIETIC STEM-CELLS; BONE-MARROW-CELLS; HUMAN CD34(+) CELLS; G-CSF; TYROSINE KINASE; ALPHA-4; INTEGRINS; CARDIAC REPAIR;
D O I
10.1016/B978-0-12-398459-3.00011-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Progenitor cell retention and release are largely governed by the binding of stromal-cell-derived factor 1 (SDF-1) to CXC chemokine receptor 4 (CXCR4) and by alpha 4-integrin signaling. Both of these pathways are dependent on c-kit activity: the mobilization of progenitor cells in response to either CXCR4 antagonism or alpha 4-integrin blockade is impaired by the loss of c-kit kinase activity; and c-kit-kinase inactivation blocks the retention of CXCR4-positive progenitor cells in the bone marrow. SDF-1/CXCR4 and alpha 4-integrin signaling are also crucial for the retention of progenitor cells in the ischemic region, which may explain, at least in part, why clinical trials of progenitor cell therapy have failed to display the efficacy observed in preclinical investigations. The lack of effectiveness is often attributed to poor retention of the transplanted cells and, to date, most of the trial protocols have mobilized cells with injections of granulocyte colony-stimulating factor (G-CSF), which activates extracellular proteases that irreversibly cleave cell-surface adhesion molecules, including alpha 4-integrin and CXCR4. Thus, the retention of G-CSF-mobilized cells in the ischemic region may be impaired, and the mobilization of agents that reversibly disrupt SDF-1/CXCR4 binding, such as AMD3100, may improve patient response. Efforts to supplement SDF-1 levels in the ischemic region may also improve progenitor cell recruitment and the effectiveness of stem cell therapy.
引用
收藏
页码:243 / 264
页数:22
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