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[Effects of mobilization of bone marrow stem cells on regenerative potential of cardiac tissues after myocardial infarction].

OBJECTIVE
To test the potential of bone marrow stem cells mobilized by granulocyte macrophage colony stimulating factor (GM-CSF) to promote regeneration of myocyte and neovascularization in a rat model of myocardial infarction.


METHODS
A myocardial infarction model was created by ligation of the left anterior descending coronary artery in adult Sprague-Dawley rats. Then the infracted rats were randomly assigned to receive GM-CSF injection subcutaneously 50 microg x kg(-1) x day(-1) as experimental group or receive saline injection as control group. Enumeration of CD(34)(+) stem cells in peripheral blood and bone marrow was performed by flow cytometric analysis. Histologic and immunohistological staining such as Factor VIII, Ki67 and PTAH staining (phosphotungstic acid hematoxylin) was performed to assess angiogenesis and myogenesis, calculate myocardial infarction size in the heart.


RESULTS
The CD(34)(+) stem cells in the blood and bone marrow increased from Day 3, peaked between Day 7 (0.350% +/- 0.026%, 2.250% +/- 0.140%) and Day 14 (0.260% +/- 0.022%, 2.060% +/- 0.110%) in experimental group compared with control group (0.170% +/- 0.015%, 1.240% +/- 0.064%) (P < 0.01), declined on Day 28 and no difference versus control group (P > 0.05). Immunohistological staining showed apparent neovasculature formation and much more Ki67 expression in the infracted regions in experimental group (313 +/- 10, 275 +/- 5) compared with control group (264 +/- 10, 207 +/- 10) (P < 0.05). The Ki67 positive cells in the experimental hearts were significantly positively correlated with CD(34)(+) stem cells in the blood and bone marrow (r = 0.961, P = 0.019, r = 0.975, P = 0.005). Ki67 and PTAH double staining showed that the Ki67 positive nucleoli overlay the lymphocytes, fibroblasts and endothelial cells but not myocytes. No significant decrease of infracted size occurred in experimental group (P > 0.05).


CONCLUSIONS
Bone marrow and peripheral blood stem cells could be mobilized effectively by GM-CSF after myocardial infarction which could only promote neovascularization without myogenesis.