Abstract
Previous clinical studies evaluating granulocyte-colony stimulating factor (G-CSF)based stem-cell therapy showed inconsistent outcomes. We evaluated G-CSF-based stem-cell therapy in patients with acute myocardial infarction (AMI) and old myocardial infarction (OMI) in ‘Myocardial Regeneration and Angiogenesis in Myocardial Infarction with G-CSF and Intracoronary Stem Cell Infusion (MAGIC Cell)’ trials. In MAGIC Cell-1 trial, intracoronary infusion of mobilized stem cell by G-CSF is superior to G-CSF alone for improvement of left ventricular (LV) systolic function till 2 years follow-up. In MAGIC Cell-3-Drug eluting stent (DES) trial, cell infusion showed better improvement of LV systolic function and remodelling than control in AMI patients at 6 months follow-up. However, stem-cell therapy does not improve LV systolic function in OMI patients. G-CSF-based stem-cell therapy does not aggravate de novo progression of atherosclerosis while DES efficiently prevents G-CSF-based stem-cell-therapy-related restenosis. Longer-term follow-up is required to confirm prognostic impacts of stem-cell therapy in patients with myocardial infarction. Combination strategy with stem cell therapy with cytokines and genes should be introduced to enhance efficacy of current stem-cell therapy.
Highlights
In MAGIC Cell-1 trial, patients were randomized into one strategy among three: (i) granulocyte-colony stimulating factor (G-CSF) mobilization alone after PCI (n 1⁄4 10); (ii) intracoronary infusion of mobilized peripheral blood stem cell (PBSC) by G-CSF after PCI (n 1⁄4 10); and (iii) control PCI alone (n 1⁄4 10).[7,8]
This is the only study to directly compare the strategy of G-CSF mobilization alone and that of intracoronary infusion of mobilized PBSCs
During 2 years follow-up evaluation, patients in the intracoronary cell infusion group showed better improvements of left ventricular (LV) systolic function and remodelling compared with patients in the G-CSF alone group
Summary
Therapeutic application of granulocyte-colony stimulating factor (G-CSF) for stem-cell therapy has been evaluated by preclinical and clinical trials.[1,2,3,4] In addition to well-known, stem-cell mobilizing effects of G-CSF, G-CSF has several beneficial effects on salvage and healing of infarcted myocardium.[5,6] most of preclinical studies showed favourable outcomes for improvement of cardiac function with G-CSF-based stemcell therapy, results from clinical trials were inconsistent and rather disappointing.[2,3,4] We evaluated G-CSF-based stem-cell therapy in clinical trial since 2003 in ‘Myocardial Regeneration and Angiogenesis in Myocardial Infarction with G-CSF and Intracoronary Stem Cell Infusion’ (MAGIC Cell) trials.[7,8,9] In this article, we will present our data from clinical and preclinical studies and discuss the lessons from clinical trials and future directions of stem-cell therapy
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