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

Nature Clinical Practice Cardiovascular Medicine volume 3, pages S73–S77 (2006)Cite this article

Abstract

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.

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Figure 1: Flow chart and timing of study procedures in the FIRSTLINE-AMI protocol
Figure 2: Composite diagram of fractional cell distribution in two representative patients in the FIRSTLINE-AMI study at baseline (day 1) and day 7

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Authors and Affiliations

  1. Department of Cardiology,

    Christoph A Nienaber, Michael Petzsch, Hans Dieter Kleine, Heike Eckard, Matthias Freund & Hüseyin Ince

  2. stem cell project in the Department of Hematology, at Rostock University Hospital, Rostock School of Medicine, Rostock, Germany

    Christoph A Nienaber, Michael Petzsch, Hans Dieter Kleine, Heike Eckard, Matthias Freund & Hüseyin Ince

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  1. Christoph A Nienaber
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Correspondence to Christoph A Nienaber.

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Nienaber, C., Petzsch, M., Kleine, H. et al. Effects of granulocyte-colony-stimulating factor on mobilization of bone-marrow-derived stem cells after myocardial infarction in humans. Nat Rev Cardiol 3 (Suppl 1), S73–S77 (2006). https://doi.org/10.1038/ncpcardio0443

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