Effects of granulocyte colony-stimulating factor on repair of injured canine arteries.
BACKGROUND
Endothelial progenitor cells (EPCs) derived from bone marrow may differentiate into endothelial cells and participate in endothelial repair. These cells can be mobilized into peripheral blood by cytokines, including granulocyte colony-stimulating factor (G-CSF). In the present study, we investigated the effects of G-CSF on neointimal formation and restenosis in a canine model of arterial balloon injury.


METHODS
Sixteen male beagle dogs were injected subcutaneously with 20 microg x kg(-1) x d(-1) recombinant human G-CSF (n = 8) or normal saline (n = 8) for 1 week. On the fifth day of treatment, the dogs underwent renal arterial angioplasty. At 8 weeks after arterial balloon injury, angiographic observations were made and injured arteries were processed for morphometric analysis of neointimal formation.


RESULTS
Peripheral white blood cell counts were increased by 3.34-fold compared to baseline on the fifth day of administration of G-CSF. Angiographies revealed that one stenosis had occurred among the eight injured renal arteries from dogs treated with G-CSF, whereas all injured renal arteries from dogs treated with normal saline remained patent. The mean extent of stenosis among injured arteries was 18.3% +/- 17.9% in the G-CSF treated group compared to 12.5% +/- 7.6% in the saline treated control group (P = 0.10). G-CSF treatment slightly increased neointimal thickness (0.42 +/- 0.15 mm vs 0.25 +/- 0.06 mm, P = 0.08) with an intima to media ratio of 0.83 +/- 0.49 vs 0.54 +/- 0.18 (P = 0.11).


CONCLUSIONS
G-CSF treatment does not attenuate neointimal hyperplasia and restenosis formation in a canine model of renal arterial injury, suggesting that the therapeutic strategy for preventing restenosis by stem cell mobilization should be investigated further.
Mei
Que-lin
QL
Department of Radiology, Peking University Shenzhen Hospital, Shenzhen Medical Centre, Peking University-Hong Kong University of Sciences and Technology, Shenzhen, Guangdong 518036, China.
Yang
Jian-yong
JY
Li
Yan-hao
YH
Chen
Zai-zhong
ZZ
Yu
Hong-jian
HJ
Liu
Peng-cheng
PC
D000818:Animals; D004285:Dogs; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006965:Hyperplasia; D008297:Male; D011994:Recombinant Proteins; D012077:Renal Artery / Q000293:injuries* / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor