The impact of vascular endothelial growth factor-transfected human endothelial cells on endothelialization and restenosis of stainless steel stents.
OBJECTIVE
The purpose of this study was to investigate the effects of gene transfection of endothelial cells with vascular endothelial growth factor (VEGF) on re-endothelialization and inhibiting in-stent restenosis.


METHODS
Stents coated with human umbilical vein endothelial cells (HUVECs) transfected with VEGF(121) were studied both in vitro and in vivo. In vitro studies were performed using a homemade extracorporeal circulation system. In vivo studies were performed using the rabbit abdominal aorta model.


RESULTS
In vitro studies confirmed that VEGF(121)-transfected cells adhered on the surface of stainless steel stents with over 90% of the surface covered within 24 hours of seeding. In vivo results showed that VEGF(121)-transfected HUVECs-coated stents were covered with seeding cells after implanting, and almost completely covered with cells after stent implantation for 1 week. In contrast, the non-endothelialized areas of bare metal stents and glutin/poly-L-lysine-coated stents were covered at 4 weeks, and the monolayers of cells were not observed, but fragile neointima was found on the surface. After 12 weeks, VEGF(121)-transfected HUVECs-coated stents significantly reduced the neointima area (0.78 ± 0.03 mm(2)) and stenosis (15.69 ± 2.61%) as compared with those for bare metal stents (neointima area = 2.26 ± 0.67 mm(2); the percentage of stenosis = 47.55 ± 7.10%;P < .01) and glutin/poly-L-lysine-coated stents (neointima area = 1.40 ± 0.37 mm(2); the percentage of stenosis = 31.37 ± 8.18%;P < .01).


CONCLUSIONS
In this small animal study, VEGF transfected human endothelial cells, when coated on stainless steel stents, reduce neointimal hyperplasia, promote endothelialization, and reduce in-stent restenosis. Additional studies with this technology are necessary to determine its ultimate utility in improving stents performance.
Key Laboratory of Biorheological Science and Technology, Bioengineering College of Chongqing University, Chongqing, China.
Chaojun
C
Tang
Guixue
G
Wang
Xue
X
Wu
Zhenggong
Z
Li
Yang
Y
Shen
James C-M
JC
Lee
Qingsong
Q
Yu
D017130:Angioplasty / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology*; D001018:Aortic Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D003251:Constriction, Pathologic; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D006965:Hyperplasia; D008297:Male; D011474:Prosthesis Design; D011817:Rabbits; D013193:Stainless Steel; D015607:Stents; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D020099:Coated Materials, Biocompatible; D042461:Vascular Endothelial Growth Factor A; D013193:Stainless Steel