BACKGROUND: Transplantation of marrow stromal cells (MSC) has been shown to 
improve heart perfusion and cardiac function after ischemia. Erythropoietin 
(EPO) is capable of inducing angiogenesis and inhibiting cell apoptosis. The aim 
of this study was to investigate the effect of EPO on the therapeutic potency of 
MSC transplantation in a rat model of myocardial infarction.
METHODS: MSC viability was detected by MTT and flow cytometry following culture 
in serum-free medium for 24 h with or without EPO. Release of vascular 
endothelial growth factor (VEGF) by MSC incubated with different doses of EPO 
was assayed using ELISA. Immediately after coronary ligation, autologous MSC (3 
x 10(6) cells) were injected into the ischemic myocardium (MSC and MSC-EPO 
groups). EPO (3,000 U/kg body weight) was injected daily for 3 consecutive days 
starting 1 day prior to ligation. The same EPO dose was also injected for 
consecutive 3 days starting 15 days after surgery (EPO and MSC-EPO groups). 
Control animals were injected saline solution for the same time period. Cardiac 
function was assessed by echocardiography 2 and 21 days after surgery, 
respectively. Western blot and immunohistological assessments were performed to 
examine the effects of treatments.
RESULTS: In vitro, EPO inhibited MSC apoptosis induced by serum-free medium and 
increased vascular endothelial growth factor (VEGF) release by MSC. In vivo, 
cardiac infarct size was significantly smaller, cardiac function significantly 
improved, and capillary density obviously higher in the MSC and EPO groups than 
in the control group. Combined treatment with EPO infusion and MSC 
transplantation demonstrated a further decrease in infarct size, a further 
improvement in cardiac function, and a further increase in capillary density 
compared with MSC or EPO alone. Furthermore, a higher ratio of phosphorylated 
Akt to total Akt was measured by Western blot; Bcl-2 was upregulated and Bax was 
downregulated by immunohistochemistry in the MSC-EPO group compared to the other 
three groups.
CONCLUSION: Transplantation of MSC combined with EPO infusion is superior to MSC 
monotherapy for angiogenesis and cardiac function recovery.