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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Stem cell mobilization utilizing granulocyte colony stimulating factor in advanced chronic heart failure: lessons from a pilot study

Jacob Joseph1,2,*, Paulette Mehta3,6, Asem Rimawi3,6, Michele Cottler-Fox4,6, Anjan Sinha3,6, Balkrishna Mansingh3,6, Eugene S. Smith, III3,6 and Jawahar L. Mehta3,5,6

1 Department of Medicine, Cardiology Section (111), VA Boston Healthcare System, 1400 VFW Parkway, West Roxbury, Boston, MA 02132, USA
2 Department of Medicine, Boston University School of Medicine, Boston, MA, USA
3 Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA
4 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
5 Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
6 Central Arkansas Veterans Healthcare System, Little Rock, AR, USA

* Corresponding author. Tel: +1 857 203 6841; fax: +1 857 203 5550, E-mail address: jacob.joseph{at}med.va.gov

Mobilizing haematopoietic progenitor cells (HPC) to repair the failing heart is a promising intervention to halt the progression of this deadly disease. We postulated that low doses of granulocyte colony stimulating factor (GCSF) could successfully mobilize HPC in advanced systolic heart failure and lead to beneficial effects. In a pilot study involving patients with advanced systolic heart failure, we established that a low dose (5 µg/kg/day for 5 days) of GCSF was sufficient to mobilize HPC into the peripheral blood in adequate numbers (>10 cells/µL) in spite of advanced heart failure and subject age. A striking observation was the significant elevation of plasma interleukin-10 levels in response to GCSF, without any change in tumour necrosis factor-{alpha} or interferon-{gamma} levels. Left ventricular function improved significantly in subjects with ischaemic cardiomyopathy at 9 months after a single 5-day cycle of GCSF. Our results suggest the potential for improving left ventricular function in advanced systolic heart failure utilizing GCSF.

Key Words: Stem cells • Heart failure • Ventricle • Cytokines


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