Circulation, Vol 80, 1347-1353, Copyright © 1989 by American Heart Association
DA Dichek, RF Neville, JA Zwiebel, SM Freeman, MB Leon and WF Anderson
The use of intravascular stents may be limited by both local thrombosis and
restenosis due to intimal proliferation. In an effort to provide solutions
to these problems, we seeded stents with genetically engineered endothelial
cells in vitro. Using retroviral-mediated gene transfer, we inserted the
gene for either bacterial beta-galactosidase or human tissue-type
plasminogen activator (t-PA) into cultured sheep endothelial cells. The
endothelial cells were seeded onto stainless steel stents and grown until
the stents were covered. Expression of intracellular beta-galactosidase and
high level secretion of t-PA were demonstrated both before and after the
transduced cells were seeded onto the stents. Eight stents were expanded by
in vitro balloon inflation, with observation of the seeded endothelial
layer both prior to and after expansion. Most of the endothelial cells
remained on the stents after balloon inflation. We conclude that
intravascular stents can be coated with a layer of genetically engineered
endothelial cells that can be either specifically labeled or made to
secrete high levels of a therapeutic protein. Much of the layer of
genetically engineered cells remains after the expansion of the stent in
vitro. In vivo implantation of stents coated with genetically engineered
endothelial cells may allow 1) introduction of genetically engineered
endothelial cells directly into the vascular wall and 2) improvement of
stent function through localized delivery of anticoagulant, thrombolytic,
or antiproliferative molecules.
ARTICLES
Seeding of intravascular stents with genetically engineered endothelial cells
Laboratory of Molecular Hematology, National Institutes of Health, Bethesda, Maryland 20892.
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