SDF-1α as a therapeutic stem cell homing factor in myocardial infarction.
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.
Department of Cardiovascular and Metabolic Disease Research, Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Str. 10, D-13125 Berlin, Germany.
Santhosh K
SK
Ghadge
Silke
S
Mühlstedt
Cemil
C
Ozcelik
Michael
M
Bader
D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018925:Chemokines / Q000494:pharmacology / Q000502:physiology; D002986:Clinical Trials as Topic; D006321:Heart / Q000503:physiopathology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D019718:Receptors, CXCR4 / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*
D054377:Chemokine CXCL12; D018925:Chemokines; D019718:Receptors, CXCR4