Seeding of intravascular stents by the xenotransplantation of genetically modified endothelial cells.
A novel approach of cell seeding of stents using xenotransplanted endothelium is proposed. The advantages of this approach are that these doubly transgenic animals will provide a limitless supply of endothelial cells producing controllable levels of active compound. These foreign cells will act as Trojan horses, graciously accepted at face value by the host organism, but capable of modifying the pathophysiological response to vessel damage, typified by the process of restenosis. Once implanted, the production of the bioactive compound is under exogenous control by means of 'designer' genes coding for modified cell surface receptors, which are introduced with the transgene to provide controllable levels of compound. Interaction of an orally administered compound with the modified cell receptor will switch on the transgene, while in its absence the transgene remains dormant. We have been able to show the feasibility this type of approach has for other animal species, and it shows great potential for application to humans.
Thoraxcenter, University Hospital Rotterdam, The Netherlands.
M J
MJ
Kutryk
L M
LM
van Dortmont
R P
RP
de Crom
A W
AW
van der Kamp
P D
PD
Verdouw
W J
WJ
van der Giessen
D000818:Animals; D030801:Animals, Genetically Modified; D003327:Coronary Disease / Q000473:pathology / Q000628:therapy; D003331:Coronary Vessels / Q000473:pathology*; D004730:Endothelium, Vascular / Q000166:cytology*; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D017354:Point Mutation; D055502:Secondary Prevention; D015607:Stents; D014183:Transplantation, Heterologous
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III