Mobilization of bone marrow-derived stem cells (BMCs) was shown to have 
protective effects after myocardial infarction (MI). However, the classical 
mobilizing agent, granulocyte-colony stimulating factor (G-CSF) relapsed after 
revealing an impaired homing capacity. In the search for superior cytokines, 
erythropoietin (EPO) appears to be a promising agent. Therefore, we analyzed in 
a murine model of surgically induced MI the influence of EPO treatment on 
survival and functional parameters as well as BMC mobilization, homing, and 
effect on resident cardiac stem cells (CSCs). Human EPO was injected 
intraperitoneally after ligation of the left anterior descendens (LAD) for 3 
days with a total dose of 5000 IU/kg 6 and 30 days after MI, and pressure volume 
relationships were investigated in vivo. Cardiac tissues were analyzed by 
histology. To show the effect on BMCs and CSCs, FACS analyses were performed. 
Homing factors were analyzed by quantitative reverse transcription-polymerase 
chain reaction (qRT-PCR) and ELISA. EPO-treated animals showed a significant 
improvement of survival post-MI (62 vs. 36%). At days 6 and 30, all hemodynamic 
parameters associated with attenuated remodeling, enhanced neovascularization, 
and diminished apoptotic cells in the peri-infarct area were improved. BMC 
subpopulations (CD31(+), c-kit(+), and Sca-1(+) cells) were mobilized, and 
homing of Sca-1(+) and CXCR4(+) BMCs toward an SDF-1 gradient into the ischemic 
myocardium was enhanced. However, there was no beneficial effect on CSCs. We 
have shown that EPO application after MI shows cardioprotective effects. This 
may be explained by mobilization of BMCs, which are homing via the CXCR-4/SDF-1 
axis. However, EPO has no beneficial effects on resident CSCs. Therefore, new 
treatment regimes using EPO together with other agents may combine complementary 
beneficial effects preventing ischemic cardiomyopathy.