The potential of in vivo vascular tissue engineering for the treatment of vascular thrombosis: A preliminary report

Michael D. Kuo, Jacob M. Waugh, Eser Yuksel, Adam B. Weinfeld, Mehtap Yuksel, Michael D. Dake

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

OBJECTIVE. Current gene therapy and tissue engineering protocols suffer from a number of inherent limitations. In this study, we examine the feasibility of a new approach for the treatment of vascular thrombosis: in vivo tissue engineering. MATERIALS AND METHODS. Rabbit femoral veins were transfected in situ with either a previously characterized adenoviral- construct-expressing tissue plasminogen activator or a viral (adenoviral- construct-expressing β-galactosidase) or nonviral (buffer) control and used as cross sections (n = 3). Treated veins were then 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 downstream 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 evaluated. RESULTS. The engineered vein graft showed a significant reduction in thrombus formation within both the graft and the downstream artery relative to nonvital (buffer) and viral (adenoviral-Rous sarcoma virus β- galactosidase [Adv/RSV-βgal]) controls. Underlying endothelial cell transfection efficiency of 90% was observed in viral controls (Adv/RSV- βgal). A 2.4-fold increase in smooth muscle α-actin positive cells in the engineered vein graft was seen compared with nonviral (phosphate-buffered saline) controls. A 10-fold increase in smooth muscle α-actin-positive cells in the engineered vein graft relative to viral (Adv/RSV-βgal) controls was also observed. CONCLUSION. 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.

Original languageEnglish (US)
Pages (from-to)553-558
Number of pages6
JournalAmerican Journal of Roentgenology
Volume171
Issue number3
StatePublished - Sep 1 1998
Externally publishedYes

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Tissue Engineering
Blood Vessels
Thrombosis
Transplants
Veins
Galactosidases
Rous sarcoma virus
Arteries
Therapeutics
Genetic Therapy
Transfection
Smooth Muscle
Actins
Buffers
Molecular Medicine
Rabbits
Femoral Vein
Tissue Plasminogen Activator
Femoral Artery
Smooth Muscle Myocytes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

The potential of in vivo vascular tissue engineering for the treatment of vascular thrombosis : A preliminary report. / Kuo, Michael D.; Waugh, Jacob M.; Yuksel, Eser; Weinfeld, Adam B.; Yuksel, Mehtap; Dake, Michael D.

In: American Journal of Roentgenology, Vol. 171, No. 3, 01.09.1998, p. 553-558.

Research output: Contribution to journalArticle

Kuo, Michael D. ; Waugh, Jacob M. ; Yuksel, Eser ; Weinfeld, Adam B. ; Yuksel, Mehtap ; Dake, Michael D. / The potential of in vivo vascular tissue engineering for the treatment of vascular thrombosis : A preliminary report. In: American Journal of Roentgenology. 1998 ; Vol. 171, No. 3. pp. 553-558.
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abstract = "OBJECTIVE. Current gene therapy and tissue engineering protocols suffer from a number of inherent limitations. In this study, we examine the feasibility of a new approach for the treatment of vascular thrombosis: in vivo tissue engineering. MATERIALS AND METHODS. Rabbit femoral veins were transfected in situ with either a previously characterized adenoviral- construct-expressing tissue plasminogen activator or a viral (adenoviral- construct-expressing β-galactosidase) or nonviral (buffer) control and used as cross sections (n = 3). Treated veins were then 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 downstream 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 evaluated. RESULTS. The engineered vein graft showed a significant reduction in thrombus formation within both the graft and the downstream artery relative to nonvital (buffer) and viral (adenoviral-Rous sarcoma virus β- galactosidase [Adv/RSV-βgal]) controls. Underlying endothelial cell transfection efficiency of 90{\%} was observed in viral controls (Adv/RSV- βgal). A 2.4-fold increase in smooth muscle α-actin positive cells in the engineered vein graft was seen compared with nonviral (phosphate-buffered saline) controls. A 10-fold increase in smooth muscle α-actin-positive cells in the engineered vein graft relative to viral (Adv/RSV-βgal) controls was also observed. CONCLUSION. 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.",
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N2 - OBJECTIVE. Current gene therapy and tissue engineering protocols suffer from a number of inherent limitations. In this study, we examine the feasibility of a new approach for the treatment of vascular thrombosis: in vivo tissue engineering. MATERIALS AND METHODS. Rabbit femoral veins were transfected in situ with either a previously characterized adenoviral- construct-expressing tissue plasminogen activator or a viral (adenoviral- construct-expressing β-galactosidase) or nonviral (buffer) control and used as cross sections (n = 3). Treated veins were then 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 downstream 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 evaluated. RESULTS. The engineered vein graft showed a significant reduction in thrombus formation within both the graft and the downstream artery relative to nonvital (buffer) and viral (adenoviral-Rous sarcoma virus β- galactosidase [Adv/RSV-βgal]) controls. Underlying endothelial cell transfection efficiency of 90% was observed in viral controls (Adv/RSV- βgal). A 2.4-fold increase in smooth muscle α-actin positive cells in the engineered vein graft was seen compared with nonviral (phosphate-buffered saline) controls. A 10-fold increase in smooth muscle α-actin-positive cells in the engineered vein graft relative to viral (Adv/RSV-βgal) controls was also observed. CONCLUSION. 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.

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