Administration of the bifunctional SDF1-GPVI fusion protein in a mouse model of myocardial infarction enhanced recruitment of bone marrow cells, reduced infarct size, and preserved cardiac function.
BACKGROUND: CXCR4-positive bone marrow cells (BMCs) are critically involved in cardiac repair mechanisms contributing to preserved cardiac function. Stromal cell-derived factor-1 (SDF-1) is the most prominent BMC homing factor known to augment BMC engraftment, which is a limiting step of stem cell-based therapy. After myocardial infarction, SDF-1 expression is rapidly upregulated and promotes myocardial repair. METHODS AND RESULTS: We have established a bifunctional protein consisting of an SDF-1 domain and a glycoprotein VI (GPVI) domain with high binding affinity to the SDF-1 receptor CXCR4 and extracellular matrix proteins that become exposed after tissue injury. SDF1-GPVI triggers chemotaxis of CXCR4-positive cells, preserves cell survival, enhances endothelial differentiation of BMCs in vitro, and reveals proangiogenic effects in ovo. In a mouse model of myocardial infarction, administration of the bifunctional protein leads to enhanced recruitment of BMCs, increases capillary density, reduces infarct size, and preserves cardiac function. CONCLUSIONS: These results indicate that administration of SDF1-GPVI may be a promising strategy to treat myocardial infarction to promote myocardial repair and to preserve cardiac function.
Ziégler et al. (Fri,) conducted a other in Myocardial infarction. SDF1-GPVI fusion protein was evaluated on Recruitment of BMCs, capillary density, infarct size, and cardiac function. Administration of the bifunctional SDF1-GPVI fusion protein in a mouse model of myocardial infarction enhanced recruitment of bone marrow cells, reduced infarct size, and preserved cardiac function.