Bj. Ballermann et Mj. Ott, ADHESION AND DIFFERENTIATION OF ENDOTHELIAL-CELLS BY EXPOSURE TO CHRONIC SHEAR-STRESS - A VASCULAR GRAFT MODEL, Blood purification, 13(3-4), 1995, pp. 125-134
Long-term patency of artificial vascular grafts for hemodialysis acces
s and for bypass or interposition in small caliber arteries is limited
due to neointimal hyperplasia and associated graft thrombosis. Given
the anticoagulant and vasodilatory properties of endothelial cells, th
ese problems could be partially overcome if grafts were seeded with an
adherent monolayer of differentiated endothelial cells, prior to impl
antation. Endothelial cells in vivo are highly adherent and can resist
disruption by hemodynamic shear stress at levels that far exceed phys
iological conditions. Endothelial cells in vivo also are highly differ
entiated, with an organized cytoskeleton, Weibel-Palade bodies, and ba
sal stress fibers with focal adhesion plaques. In cell culture, endoth
elial cells rapidly lose many of their differentiated features, and en
dothelial cells on artificial surfaces, like vascular graft material,
are not sufficiently adherent or differentiated to resist physiologic
shear stress. We find that endothelial cells exposed to chronic shear
stress in vitro, applied in a stepwise fashion over several days, are
induced to become tightly adherent to the substratum and exhibit more
differentiated features. Thus, pre-conditioning of endothelial cells s
eeded on vascular grafts with stepwise shear stress in vitro could be
used to improve endothelial cell retention and differentiation for sub
sequent in vivo use.