SDF-1α as a therapeutic stem cell homing factor in myocardial infarction

SK Ghadge, S Mühlstedt, C Özcelik, M Bader - Pharmacology & …, 2011 - Elsevier
SK Ghadge, S Mühlstedt, C Özcelik, M Bader
Pharmacology & therapeutics, 2011Elsevier
Myocardial infarction is associated with persistent muscle damage, scar formation and
depressed cardiac performance. Recent studies have demonstrated the clinical significance
of stem cell-based therapies after myocardial infarction with the aim to improve cardiac
remodeling and function by inducing the reconstitution of functional myocardium and
formation of new blood vessels. Stem cell homing signals play an important role in stem cell
mobilization from the bone marrow to the ischemic cardiac environment and are therefore …
Myocardial infarction is associated with persistent muscle damage, scar formation and depressed cardiac performance. Recent studies have demonstrated the clinical significance of stem cell-based therapies after myocardial infarction with the aim to improve cardiac remodeling and function by inducing the reconstitution of functional myocardium and formation of new blood vessels. Stem cell homing signals play an important role in stem cell mobilization from the bone marrow to the ischemic cardiac environment and are therefore crucial for myocardial repair. To date, the most prominent stem cell homing factor is the chemokine SDF-1α/CXCL12. This protein was shown to be significantly upregulated in many experimental models of myocardial infarction and in patients suffering from ischemic cardiac diseases, suggesting the involvement in the pathophysiology of these disorders. A number of studies focused on manipulating SDF-1α and its receptor CXCR4 as central regulators of the stem cell mobilization process. Targeted expression of SDF-1α after myocardial infarction was shown to result in increased engraftment of bone marrow-derived stem cells into infarcted myocardium. This was accompanied by beneficial effects on cardiomyocyte survival, neovascularization and cardiac function. Thus, the SDF-1/CXCR4 axis seems to be a promising novel therapeutic approach to improve post-infarction therapy by attracting circulating stem cells to remain, survive and possibly differentiate in the infarct area. This review will summarize clinical trials of stem cell therapy in patients with myocardial infarction. We further discuss the basic findings about SDF-1α in stem cell recruitment and its therapeutic implications in experimental myocardial infarction.
Elsevier