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(Circulation. 2007;116:I-24 – I-30.)
© 2007 American Heart Association, Inc.

Cell Transplantation and Tissue Regeneration

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

Rasmus Sejersten Ripa, MD; Mandana Haack-Sørensen, MSc; Yongzhong Wang, MD, PhD; Erik Jørgensen, MD; Steen Mortensen, Tech; Lene Bindslev, MSc, PhD; Tina Friis, MSc, PhD; Jens Kastrup, MD, DMSc

From the Department of Cardiology, The Heart Centre, University Hospital Rigshospitalet, Copenhagen, Denmark.

Correspondence to Jens Kastrup MD, DMSc, Medical Department B, Cardiac Catheterization Laboratory 2014, The Heart Centre, University Hospital Rigshospitalet, DK-2100 Copenhagen Ø, Denmark. E-mail jkastrup{at}rh.regionh.dk

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 µg/kg/d) or placebo. Over 7 days, the myocardium was exposed to 25x10⁹ G-CSF mobilized CD34⁺ cells, compared with 3x10⁹ cells in placebo patients (P<0.001); and to 4.9x10¹¹ mesenchymal stem cells, compared with 2.0x10¹¹ 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 x10^–3, P<0.001 when compared with placebo), whereas the fraction of putative mesenchymal stem cells/leukocyte decreased (from 22±17 to 14±11 x10^–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.

Key Words: stem cells • angiogenesis • heart failure • magnetic resonance imaging • myocardial infarction