The effect of stem cell mobilization by granulocyte-colony stimulating factor on neointimal hyperplasia and endothelial healing after vascular injury with bare-metal versus paclitaxel-eluting stents.
OBJECTIVE
The goal of this study was to investigate the effect of mobilized stem cells by granulocyte-colony stimulating factor (G-CSF) on neointimal growth, the biologic impact on vascular healing process, and the utility of paclitaxel-eluting stent (PES) in this circumstance.


BACKGROUND
Questions have been raised on the safety of stem cell mobilization because of the tendency of neointimal overgrowth in a recent clinical trial, despite improvement of cardiac function.


METHODS
Rabbits underwent iliac artery injury with bare-metal stent (BMS) or PES and then received rhG-CSF or placebo for 6 days. Morphometric analysis and scanning electron microscopy for re-endothelialization were performed. The characteristics of mobilized peripheral blood mononuclear cells were determined in vitro, and the fate of these cells was evaluated by re-infusion with tagging in vivo.


RESULTS
At day 60 after stenting, neointimal overgrowth was observed at BMS with G-CSF. The tendency of neointimal overgrowth was substantially reduced on PES. Intriguingly, the delayed endothelial recovery on PES was restored to normal after G-CSF treatment. The G-CSF increased not only the endothelial progenitor cells, but also putative smooth muscle progenitor cells. Paclitaxel, at working concentration, preferentially inhibited proliferation of smooth muscle lineage cells rather than endothelial lineage cells.


CONCLUSIONS
Our findings demonstrate that G-CSF mobilizes putative vascular progenitor cells in peripheral blood, which induces neointimal overgrowth at stented vasculature. Unique differential action of paclitaxel results in the enhanced endothelial healing with reduced neointimal growth after G-CSF treatment, suggesting that drug-eluting stents might be the optimal modality for revascularization in cytokine-based stem cell therapy.
Cho
Hyun-Jai
HJ
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Kim
Tae-Youn
TY
Cho
Hyun-Ju
HJ
Park
Kyung-Woo
KW
Zhang
Shu-Ying
SY
Kim
Ji-Hyun
JH
Kim
Sung-Hwan
SH
Hahn
Joo-Yong
JY
Kang
Hyun-Jae
HJ
Park
Young-Bae
YB
Kim
Hyo-Soo
HS
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D002454:Cell Differentiation; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000473:pathology*; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D017239:Paclitaxel / Q000008:administration & dosage; D011817:Rabbits; D011994:Recombinant Proteins; D015607:Stents; D017539:Tunica Intima / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel