Bone Marrow-derived mesenchymal cell mobilization by granulocyte-colony stimulating factor after acute myocardial infarction - Results from the stem cells in myocardial infarction (STEMMI) trial

Background - Granulocyte-colony stimulating factor (G-CSF) after myocardial infarction does not affect systolic function when compared with placebo. In contrast, intracoronary infusion of bone marrow cells appears to improve ejection fraction. We aimed to evaluate the G-CSF mobilization of subsets of stem cells. Methods and Results - We included 78 patients (62 men; 56 +/- 8 years) with ST-elevation myocardial infarction treated with primary percutaneous intervention <12 hours after symptom onset. Patients were randomized to double-blind G-CSF (10 mu g/kg/d) or placebo. Over 7 days, the myocardium was exposed to 25 x 10(9) G-CSF mobilized CD34(+) cells, compared with 3 x 10(9) cells in placebo patients (P < 0.001); and to 4.9 x 10(11) mesenchymal stem cells, compared with 2.0 x 10(11) in the placebo group (P < 0.001). The fraction of CD34(+) cells/leukocyte increased during G-CSF treatment (from 0.3 +/- 0.2 to 1.1 +/- 0.9 x 10(-3), P < 0.001 when compared with placebo), whereas the fraction of putative mesenchymal stem cells/leukocyte decreased (from 22 +/- 17 to 14 +/- 11 x 10(-3), P = 0.01 when compared with placebo). An inverse association between number of circulating mesenchymal stem cells and change in ejection fraction was found (regression coefficient -6.8, P = 0.004), however none of the mesenchymal cell subtypes analyzed, were independent predictors of systolic recovery. Conclusions - The dissociated pattern for circulating CD34(+) and mesenchymal stem cells could be attributable to reduced mesenchymal stem cell mobilization from the bone marrow by G-CSF, or increased homing of mesenchymal stem cells to the infarcted myocardium. The inverse association between circulating mesenchymal stem cells and systolic recovery may be of clinical importance and should be explored further.