Endothelial cell seeding fails to attenuate intimal thickening in balloon-injured rabbit arteries.
BACKGROUND
Restenosis of arteries or bypass grafts after vascular reconstruction is a common clinical entity that significantly limits long-term patency. This process, termed intimal hyperplasia (IH), is characterized by smooth muscle cell proliferation in the intima and subsequent accumulation of intercellular matrix. This study was designed to test the hypothesis that endothelial cell (EC) seeding of acutely injured arteries accelerates reendothelialization of the flow surface and limits the development of IH.


METHODS
ECs were harvested from jugular veins of New Zealand white rabbits (n = 13) and were amplified in tissue culture. Each animal subsequently underwent bilateral balloon catheter injury of the iliofemoral arteries; one side was immediately seeded with cultured autologous ECs at supraconfluent density, whereas the contralateral vessel served as a nonseeded control. Animals were killed 33 +/- 5 days after balloon injury. Intimal thickening was quantitated on histologic sections of vessels (three sections per vessel, total of 60 sections) and percent endothelialization was assessed by SEM; measurements were obtained by use of computer-aided morphometry performed by a blinded observer. Data were analyzed by use of a paired t test for comparison between seeded and control vessels.


RESULTS
Seeded vessels exhibited a greater degree of reendothelialization (93.9% +/- 7.6% of the surface) than their unseeded counterparts (65.1% +/- 22.5%, p < 0.01). Intimal cross-sectional area and the ratio of intimal area to medial area were not significantly different between seeded and control vessels (intima: 0.32 +/- 0.19 vs 0.37 +/- 0.11 mm2, p = 0.28; intimal area to medial area ratio: 0.84 +/- 0.35 vs 1.02 +/- 0.2, p = 0.24).


CONCLUSIONS
We conclude that seeding with autologous venous ECs accelerated restoration of the endothelial monolayer but failed to attenuate IH in balloon-injured rabbit arteries. Further studies are necessary to determine the functional properties of seeded endothelium and to examine the effect of EC seeding on intimal thickening in other clinically relevant models.
Conte
M S
MS
Department of Surgery, Brigham and Women's Hospital Boston, MA.
Choudhury
R P
RP
Shirakowa
M
M
Fallon
J T
JT
Birinyi
L K
LK
Choudhry
R P
RP
Choudury
R P
RP
D000818:Animals; D001158:Arteries / Q000293:injuries* / Q000473:pathology / Q000648:ultrastructure; D002404:Catheterization / Q000009:adverse effects*; D017690:Cell Transplantation; D004730:Endothelium, Vascular / Q000166:cytology*; D006965:Hyperplasia / Q000517:prevention & control; D007083:Iliac Artery / Q000293:injuries; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D017539:Tunica Intima / Q000473:pathology* / Q000648:ultrastructure