Our results provide the first evidence that there might be a dependency on epicardial delivery and/or intramyocardial dose for the early EPO-mediated induction of the SDF-1/CXCR4 axis, the increased expression of EPC marker CD34, the enrichment of the early post-ischemic cardiac mesenchyme with highly angiogenetic cardiac MSCs and the enhanced angiogenesis in the ischemic heart. Here, CXCR4 is linked to benign neoplasm.