THE POTENTIAL OF IN-VIVO VASCULAR TISSUE ENGINEERING FOR THE TREATMENT OF VASCULAR THROMBOSIS - A PRELIMINARY-REPORT

OBJECTIVE. Current gene therapy and tissue engineering protocols suffe r from a number of inherent limitations. In this study, we examine the feasibility of a new approach for the treatment of vascular thrombosi s: in vivo tissue engineering. MATERIALS AND METHODS. Rabbit femoral v eins were transfected in situ with either a previously characterized a denoviral-construct-expressing tissue plasminogen activator or a viral (adenoviral-construct-expressing beta-galactosidase) or nonviral (buf fer) control and used as cross sections (n = 3). Treated veins were th en harvested and grafted into the ipsilateral common femoral artery as an interposition vein graft. A potent stimulus for thrombus formation was then introduced into the recipient artery downstream of the graft . Six days later, the rabbits were sacrificed, and the grafts and down stream arteries were harvested. Vessel segments were then examined for thrombus according to defined anatomic zones. Transfection efficiency and presence of smooth muscle cells in the vein graft were also evalu ated. RESULTS. The engineered vein graft showed a significant reductio n in thrombus formation within both the graft and the downstream arter y relative to nonviral (buffer) and viral (adenoviral-Rous sarcoma vir us beta-galactosidase [Adv/RSV-beta gal]) controls. Underlying endothe lial cell transfection efficiency of 90% was observed in viral control s (Adv/RSV-beta gal). A 2.4-fold increase in smooth muscle alpha-actin positive cells in the engineered vein graft was seen compared with no nviral (phosphate-buffered saline) controls. A 10-fold increase in smo oth muscle alpha-actin-positive cells in the engineered vein graft rel ative to viral (Adv/RSV-beta gal) controls was also observed. CONCLUSI ON. In vivo tissue engineering is a new paradigm in molecular medicine that is a viable alternative to conventional gene therapy and tissue engineering for the treatment of vascular thrombosis.