Background: It has been reported previously that granulocyte colony-stimulating factor (GCSF) injection improves infarcted heart function, but the mechanism remains unclear. In this study we sought to determine whether GCSF-mobilized bone marrow cells could regenerate neo-myocardium and repair doxorubicin-induced cardiomyopathy.
Methods: C57BL/6 mice were irradiated and bone marrow cells (BMC; 1 x 10(6)) from green fluorescent protein (GFP) mice (GFP-BMC) were transplanted intravenously, followed by splenectomy. Doxorubicin (2.5 mg/kg, 6 times for 2 weeks) was administered intraperitoneally 2 weeks later. GCSF (50 microg/kg/day for 8 days) was administered sub-cutaneously after doxorubicin injection (Group I, n = 11) and 3 weeks later (Group II, n = 8), and saline was injected in Group III animals (n = 8). Eight weeks after doxorubicin injection, the excised hearts were studied immunologically and electron microscopically.
Results: Survival rates were 81.8% in Group I, 50.0% in Group II and 62.5% in Group III. The number of GFP-BMC in Group I (15.4 +/- 7.4 per high-power field) was highest (p < 0.05). In all groups, cardiac troponin I-positive cells derived from GFP-BMC were observed in the hearts. GFP-BMC in hearts stained positively against cardiac troponin I (4.3 +/- 2.5%), myosin heavy chain (5.0 +/- 4.3%), atrial natriuretic peptide (ANP; 3.9 +/- 2.4%) and connexin 43 (11.9 +/- 7.3%) in Group I. Myofibrils, mitochondria and fundamental architecture were almost all preserved in Group I, whereas hearts were severely damaged in Groups II and III.
Conclusions: Bone marrow was shown to be one of the sources of regenerated cardiomyocytes in the doxorubicin-induced cardiomyopathic heart. Early administration of GCSF enhanced the migration of bone marrow cells into the heart, and attenuated the cardiotoxicity of doxorubicin.