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

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) α4-integrin signaling. Both these pathways dependent on c-kit activity: mobilization progenitor cells in response either CXCR4 antagonism or blockade is impaired loss kinase activity; c-kit–kinase inactivation blocks CXCR4-positive bone marrow. SDF-1/CXCR4 signaling also crucial for ischemic region, which may explain, at least part, why clinical trials therapy have failed display efficacy observed preclinical investigations. The lack effectiveness often attributed poor transplanted and, date, most trial protocols mobilized with injections granulocyte colony-stimulating (G-CSF), activates extracellular proteases that irreversibly cleave cell-surface adhesion molecules, including CXCR4. Thus, G-CSF-mobilized region be impaired, agents reversibly disrupt binding, such as AMD3100, improve patient response. Efforts supplement SDF-1 levels recruitment stem therapy.