Abstract 3247: Mobilization of CD34-Positive Bone Marrow-Derived Cells After Coronary Stent Implantation: Impact on Restenosis
Backgrounds: Recently, there is accumulating evidence that bone marrow-derived stem cells are capable of differentiating into vascular cells. After vascular injury, it is hypothesized that the inflammatory response triggers the mobilization of endothelial as well as smooth muscle progenitor cells from bone marrow. This study was designed to clinically assess the mobilization of bone marrow-derived cells and to assess its linkage to inflammation in post-stent local vascular injury, repair and regeneration.
Methods and Results: We performed flow cytometric analysis to evaluate circulating CD34-positive mononuclear cells and activation of integrin Mac-1 on the surface of neutrophils in 40 patients undergoing coronary stenting. In patients implanted with bare-metal stents, CD34-positive cells increased with a maximum on day 7 post-stenting. The changes in CD34-postiive cells compared to baseline before stenting were more striking in patients that developed restenosis (332±48%, P<0.01) than in patients without restenosis (148±19%, P<0.05). In contrast, CD34-positive cells (72±21%, P<0.05) decreased in patients implanted with sirolimus-eluting stents. The percent change in CD34-positive cells on day 7 relative to baseline was closely correlated with that in activated Mac-1 at 48 hr (R=0.52, P<0.01). Cell culture assay on day 7 showed that circulating mononuclear cells differentiated into CD31-positive spindle-shaped cells in patients implanted with bare-metal stents. In patients with restenosis, the mononuclear cells differentiating into a-smooth muscle actin-positive polygonal and stellate shaped-cells were also observed. In patients implanted with sirolimus-eluting stents, both types of differentiation were suppressed.
Conclusions: Stent implantation may induce differentiation of bone marrow cells into endothelial cells or smooth cells. Endothelial cells may participate in re-endothelialization, a protective reaction against vascular injury, whereas smooth muscle cells may participate in neointimal thickening and restenosis. Sirolimus-eluting stents appear to inhibit the mobilization and differentiation of bone marrow cells.