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European Heart Journal Advance Access published online on October 25, 2006
European Heart Journal, doi:10.1093/eurheartj/ehl339
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European Heart Journal © The European Society of Cardiology 2006; all rights reserved
Received June 20, 2006
Revised September 27, 2006
Accepted October 5, 2006

Review

Myocardial regeneration induced by granulocyte-colony-stimulating factor mobilization of stem cells in patients with acute or chronic ischaemic heart disease: a non-invasive alternative for clinical stem cell therapy?

Jens Kastrup 1 *, Rasmus Sejersten Ripa 2, Yongzhong Wang 2, and Erik Jørgensen 2

1 Medical Department B, Cardiac Catheterization Laboratory 2014, Department of Cardiology, The Heart Centre, University Hospital Rigshospitalet, Copenhagen, Denmark
2 Department of Cardiology, The Heart Centre, University Hospital Rigshospitalet, Copenhagen, Denmark

* To whom correspondence should be addressed.
Jens Kastrup, E-mail: jkastrup{at}rh.hosp.dk


  Abstract

Mobilization of stem cells into the peripheral circulation for myocardial regeneration using subcutaneous injections of granulocyte-colony-stimulating factor (G-CSF) has been tested in both patients with acute myocardial infarction (AMI) and patients with chronic myocardial ischaemia. G-CSF treatment seems to be safe and unblinded trials in patients with AMI were encouraging. However, larger double-blind placebo-controlled trials have not been able to demonstrate effect of G-CSF treatment. In patients with chronic myocardial ischaemia, small-unblinded G-CSF trials did not show effect on myocardial perfusion and function. In both patient populations, G-CSF did mobilize stem cells of known importance to myocardial regeneration, but there seemed to be a general lack of homing of the stem cells into the ischaemic myocardium. In AMI, factors of importance to homing of stem cells, stem cell derived factor-1, are maximally elevated in plasma 3 weeks after infarction, suggesting that this time point could be the optimal time for stem cell mobilization treatment. The known complex interaction of stem cells and cytokines for induction of vasculogenesis should be implemented in future clinical trials, to elucidate whether G-CSF mobilization of stem cells might be useful as a new regenerative treatment in patients with ischaemic heart disease.

Keywords: Stem cells; Angiogenesis; Homing; Coronary artery disease; Myocardial infarction; Ischaemia.
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