Mobilization of stem cells by granulocyte colony-stimulating factor for the regeneration of myocardial tissue after myocardial infarction

Background and objective: Animal data suggest that mobilized bone marrow cells (BMC). may contribute to tissue regeneration after myocardial infarction (MI). However the safety, feasibility and efficacy of treatment with granulocyte colony-stimulating factor (G-CSF) to mobilize BMC after acute myocardial infarction in patients is unknown. We analysed cardiac function and perfusion in 5 patients who were treated with G-CSF in addition to standard therapeutical regimen. Methods and results: 48h after successful recanalization and stent implantation in 5 patients with acute MI, the patients received 10 mug/kg bodyweight/day G-CSF subcutaneously for a mean treatment duration of 7.6 +/- 0.5 days. Peak value of CD34(+) cells, a multipotent subfraction of bone marrow cells, was reached after 5.0 +/- 0.7 days. After 3 months of follow-up global left ventricular ejection fraction (determined by radionuclid-ventriculography) increased significantly from 42.2 +/- 6.6% to 51.6 +/- 8.3% (P < 0.05). The wall motion score and the wall perfusion score (determined by ECG gated SPECT) decreased from 13.5 +/- 3.6 to 9.9 +/- 3.5 (P < 0.05) and from 9.6 +/- 2.9 to 7.0 +/- 4.5 (P < 0.05), respectively, indicating a significant improvement of myocardial function and perfusion. No severe side effects of G-CSF treatment could be observed. Malignant arrhythmias were not observed either. Conclusion: In patients with acute MI, treatment with G-CSF to mobilize BMC appears to be well tolerable under clinical conditions. Improved cardiac function and perfusion may be attributed to BMC-associated promotion of myocardial regeneration and neovascularization.