| Objective: Bone marrow stem cells transplantation is a promising novel therapy for myocardial infarction (MI). Most of the commonly used methods for cell delivery were invasive. Bone marrow stem cells mobilization is a newly-developed non-invasive cell therapy strategy. The aim of the present study was to investigate the effects of bone marrow stem cells mobilization with granulocyte-colony stimulating factor (G-CSF) on neovascularization, cardiac performance, tissue repair and ventricular remodeling in rats with acute MI using a more clinically applicable strategy (postoperation administration without splenectomy).Methods: Forty adult male SD rats were divided randomly into CSF-treated (150ug/kg-1?d-1, n =16), control (saline, n=16) and sham-operated group (n=8). G-CSF or saline was administrated subcutaneously 6 hours after induction of experimental MI for 5 days. Sham-operated rats, experienced identical surgery without ligation, were also injected with saline subcutaneously. To label the regenerated cardiomyocytes and proliferated endothelial cells (ECs) or smooth muscle cells (SMCs) after MI, bromodeoxyuridine (BrdU, 50mg/kg-1?d-1) was given to all rats intraperitoneally beginning at 2 weeks post surgery for 4 weeks. Complete blood counts and leukocytes differentiation were obtained, and the mononuclear cells (MNCs) were separated by Ficoll gradient centrifugation and labeled with anti-CD34 for FACS analysis before operation and on the postoperative 6th day. Serum level of vascular endothelial growth factor (VEGF) was examined on day 6 after operation using ELISA kits. The change in left ventricular shape and function were measured with echocardiography before, 1 day and 6 weeks after operation including septum thickness (IVS), left ventricular end-diastolic diameter (LVDD), left ventricular end-systolic diameter (LVDS), ejection fraction (EF), fractional shortening (FS) and Tei-Index, a new parameter reflecting overall heart function. Hemodynamic data was collected after the final echocardiographic assessment including systolic blood pressure (SBP), diastolic blood pressure (DBP), dp/dtmax and dp/dtmin. Rats were sacrificed at 6 weeks after operation, and heart/body weight, lung and liver wet/dry were measured. Hearts were stained with HE, Mallory's trichrome and double immunofluorescence for histologic and morphometric measurement. Results: 1) G-CSF mobilization increased significantly leukocytes, granulocytes and MNCs numbers. The number of circulating CD34+ mononulcear cells in peripheral blood (MNCCD34+, containing hematopoietic stem/precursor cells and endothelial progenitor cells) were elevated significantly by 14-fold and 6-fold after mobilization compared to the baseline level (p=0.000) and those in control MI group (p=0.000) respectively. The counts of erythrocytes and thrombocytes were similar among groups.2) Compared to the baseline level on day 1 after MI, heart function in CSF-treated MI group was improved whereas that in control MI group was deteriorated significantly 6 weeks after MI. At the 6th week post operation, significant difference was found between CSF-treated and control MI groups concerning EF (87.6 ± 3.7 % vs. 62.5 ± 13.3 %, p=0.000), FS (52.7 ± 4.9 % vs. 30.6 ± 8.8 %, p=0.001) and Tei-Index (0.228 ± 0.083 vs. 0.441 ± 0.122, p=0.007). In hemodynamic evaluation, arterial pressures was higher (SBP: 172.1 ± 19.1 mmHg vs. 130.5 ± 36.7 mmHg, p=0.021; DBP: 129.6 ± 11.1 mmHg vs. 96.7 ± 30.3 mmHg, p=0.017), dp/dtmax (4745.9 ± 1013.3 mmHg/s vs. 2994.7 ± 1078.7 mmHg/s, p=0.047) and dp/dtmin (-3328.0 ± 822.6 mmHg/s vs. -2233.8 ± 822.8 mmHg/s, p=0.094) was improved in CSF-treated MI group. Likewise, lung and liver congestions were attenuated in the CSF-treated MI group compared to the control MI group (lung wet/dry: 3.78 ± 0.16 vs. 4.27 ± 0.31, p=0.003; liver wet/dry: 3.24 ± 0.03 vs. 3.37 ± 0.14, p=0.067). 3) Left ventricle/body weight ratio (2.30 ± 0.12 vs. 2.46 ± 0.36) and right ventricle/body weight ratio (0.57 ± 0.06 vs. 0.66 ± 0.19) tended to be attenua...
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