Effects of granulocyte-colony-stimulating factor on mobilization of bone-marrow-derived stem cells after myocardial infarction in humans

Recent experimental studies have shown that granulocyte-colony-stimulating factor (G-CSF) enhanced cardiac function after infarction. The concept of direct cytokine or cell-mediated effects on postischemic myocardial function was tested in the setting of human myocardial infarction subjected to percutaneous coronary intervention. In the FIRSTLINE-AMI study 50 consecutive patients with first ST-elevation myocardial infarction were randomly assigned to receive either 10 μg/kg G-CSF for 6 days after percutaneous coronary intervention in addition to standard medication, or standard care alone. G-CSF administration led to mobilization of CD34+ mononuclear stem cells (MNCCD34+), with a 20-fold increase to 64 ±37 MNCCD34+/μl at day 6 without significant associated changes in rheology, blood viscosity or inflammatory reaction, or any major adverse effects. At 4 months the G-CSF group showed improved left ventricular ejection fraction of 54 ± 8% versus 48 ± 4% at baseline (P <0.001), and no evidence of left ventricular end-diastolic remodeling, with a diameter of 55 ± 5 mm and improved segmental wall thickening (P<0.001); conversely, in control patients left ventricular ejection fraction was 43 ± 5% at 4 months (P<0.001), with increased left ventricular end-diastolic dimension of 58 ± 4 mm (P<0.001), and no segmental wall thickening. In conclusion, the FIRSTLINE-AMI study showed that G-CSF administration and mobilization of MNCCD34+ after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of human myocardium and prevention of remodeling without evidence of aggravated atherosclerosis. © 2006 Nature Publishing Group.