Background- We, recently, reported that G-CSF mobilization with intracoronary infusion showed improved cardiac function, however, also raised a question of aggravation of restenosis. So, we investigated the impact of mobilized stem cell on bare-metal stent (BMS) restenosis, and tested efficacy of drug-eluting stent (DES).
Methods and Results- One iliac artery of hypercholesterolemic rabbits was subjected to BMS (EXPRESS짰) and contralateral iliac artery to DES (TAXUS짰). Rabbits received rhG-CSF (70關g/day) or albumin daily for 6 days, after stent deployment. After 6 day injection, in FACS analysis of peripheral blood monocytes, G-CSF significantly increased endothelial progenitor cells(CD34+, CD31+, VE-CAD+) and remarkably increased the double positive(CD31+ or VE-CAD+ and 慣-smooth muscle actin+) fraction which implied vascular progenitor cells. In serial cultures with FACS and immunocytochemical analysis, endothelial lineage cells (CD31+) were predominant with VEGF stimulation and smooth muscles (慣-smooth muscle actin+) overgrew with PDGF, and also some cells were double positive. We evaluated endothelial recovery by scanning electromicroscopy at 28 days (n=2, each group), and morphometirc analysis was performed at 60 days (n=7, each group). In the control group, DES reduced restenosis but delayed endothelial recovery, and G-CSF mobilization worsened BMS restenosis. G-CSF mobilization with DES accelerated the re-endothelialization and did not aggravate restenosis. [Morphometry of neointimal thickness (mean짹S.D.): 0.26짹0.04, 0.34짹0.04, 0.14짹0.05 and 0.19짹0.04 mm, placebo-BMS (B), G-CSF-BMS (GB), placebo-DES (D) and G-GSF-DES (GD); B vs GB, P=0.015; B vs D, P=0.001; B vs GD, P=0.036; D vs GD, P=0.36, in ANOVA with Bonferroni correction].
Conclusions- Mobilized stem cell with G-CSF aggravated BMS in-stent restenosis in moderate degree. Out data suggests that DES with G-CSF effectively inhibits accumulation of smooth muscle progenitor cells, but not endothelial progenitor cells. So, we propose, in clinical trial on revascularization and stem cell mobilization, DES be the best solution for preventing restenosis withot altering re-endothelialization.