Effects of direct infusion of bone marrow-derived progenitor cells and indirect mobilization of hematopoietic progenitor cells on atherosclerotic plaque and inflammatory process in atherosclerosis.

BACKGROUND: We sought to investigate the effects of lin-/sca+ cells, endothelial progenitor cells (EPCs) and granulocyte colony-stimulating factor (G-CSF) administration on atherosclerotic plaque progression.

METHODS: Apolipoprotein E-deficient (apoE(-/-)) mice were splenectomized and treated with high-cholesterol diet for 6 weeks in order to induce atherosclerotic plaque development. Bone marrow-derived Lin-/sca-1+ cells were isolated and further cultured to early growth endothelial progenitor cells (EPCs). Mice were divided in four groups (n=10/group) and received two intravenous injections of 5×10(5) cells (lin-/sca-1+ or EPCs), or granulocyte colony-stimulating factor (G-CSF 100 μg/kg/day) for 7 days or normal saline. The same interventions were administered to animals, which had undergone unilateral hind-limb ischemia. Effects on inflammatory parameters, lesion severity, and atherosclerotic plaque area size were assessed.

RESULTS: The administration of both G-CSF and progenitor cells significantly decreased the levels of IL-6, 6 weeks after the initiation of treatment. Atherosclerotic lesion area was reduced by G-CSF (atherosclerotic plaque area percentage 22.94%±3.68, p=0.001), by lin-/sca-1+ (23.27%±5.98, p=0.002) and cultured EPCs (23.16±4.86%, p=0.002) compared to control (32.75%±7.05). In the atherosclerotic mice that underwent limb ischemia, the atherosclerotic plaque area, was not significantly different between the treatment groups cultured EPCs-treated mice and the control group (p=NS, for all).

CONCLUSIONS: Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells decreased plaque progression and levels of inflammatory molecules in a murine model of atherosclerosis. Treatment with G-CSF, lin-/sca-1+, or EPCs may exert beneficial effects on vascular inflammation and atherosclerotic plaque progression. However, the effects are diminished in an ischemic setting.