Endograft technology

A delivery vehicle for intravascular gene therapy

Darwin Eton, Hong Yu, Yingcai Wang, Jeffrey Raines, Gary Striker, Alan Livingstone, Bernard Timothy Baxter

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Purpose: The purpose of this study was to determine whether vascular smooth muscle cells (SMCs) suffused into a bilayered stent graft retain and express a retrovirally transduced gene for 7 months in vivo. Method: SMCs harvested from dog jugular vein were retrovirally transduced to introduce genes for tissue plasminogen activator (t-PA) and β-galactosidase. These cells were then suffused into a novel dual-layered Dacron graft and cultured for 36 to 48 hours. The grafts were mounted on a Palmaz stent and balloon-expanded in the infrarenal aorta of the SMC donor dogs (n = 6). Grafts were recovered at 1, 2, 3, 4, 5, and 7 months. A control endograft suffused with SMCs transduced with only the β-galactosidase gene was placed in the dogs with grafts recovered at 2, 3, and 4 months. t-PA antigen concentration and expression were analyzed with an enzyme-linked immunosorbent assay. Results: Retained engineered SMCs (blue nuclei) were identified in the explanted grafts, neointima, and underlying aorta with X-gal staining. The t-PA antigen concentration and t-PA activity from the SMCs recovered from the grafts remained elevated for the duration of the experiment (7 months) at levels significantly higher (3.7 ± 0.2 ng/mL per 105 cells per 24 hours and 1.4 ± 0.1 IU/mL per 105 cells per 24 hours) than in control endografts (0.5 ± 0.03 ng/mL per 105 cells per 24 hours and 0.07 ± 0.00 IU/mL per 105 cells per 24 hours; P < .001). No graft stenosis was observed. Conclusion: Retrovirally engineered vascular SMCs survived the implantation trauma, repopulated each graft, migrated into the underlying aorta, and expressed the transduced genes for the 7-month duration of the experiment. This bilayered Dacron endograft model provides a platform to study direct intravascular gene therapy.

Original languageEnglish (US)
Pages (from-to)1066-1073
Number of pages8
JournalJournal of Vascular Surgery
Volume39
Issue number5
DOIs
StatePublished - Jan 1 2004

Fingerprint

Genetic Therapy
Smooth Muscle Myocytes
Technology
Transplants
Tissue Plasminogen Activator
Galactosidases
Aorta
Polyethylene Terephthalates
Dogs
Vascular Smooth Muscle
Genes
Stents
Antigens
Neointima
Jugular Veins
Cell Nucleus
Pathologic Constriction
Enzyme-Linked Immunosorbent Assay
Staining and Labeling
Wounds and Injuries

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Endograft technology : A delivery vehicle for intravascular gene therapy. / Eton, Darwin; Yu, Hong; Wang, Yingcai; Raines, Jeffrey; Striker, Gary; Livingstone, Alan; Baxter, Bernard Timothy.

In: Journal of Vascular Surgery, Vol. 39, No. 5, 01.01.2004, p. 1066-1073.

Research output: Contribution to journalArticle

Eton, D, Yu, H, Wang, Y, Raines, J, Striker, G, Livingstone, A & Baxter, BT 2004, 'Endograft technology: A delivery vehicle for intravascular gene therapy', Journal of Vascular Surgery, vol. 39, no. 5, pp. 1066-1073. https://doi.org/10.1016/j.jvs.2003.11.033
Eton D, Yu H, Wang Y, Raines J, Striker G, Livingstone A et al. Endograft technology: A delivery vehicle for intravascular gene therapy. Journal of Vascular Surgery. 2004 Jan 1;39(5):1066-1073. https://doi.org/10.1016/j.jvs.2003.11.033
Eton, Darwin ; Yu, Hong ; Wang, Yingcai ; Raines, Jeffrey ; Striker, Gary ; Livingstone, Alan ; Baxter, Bernard Timothy. / Endograft technology : A delivery vehicle for intravascular gene therapy. In: Journal of Vascular Surgery. 2004 ; Vol. 39, No. 5. pp. 1066-1073.
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abstract = "Purpose: The purpose of this study was to determine whether vascular smooth muscle cells (SMCs) suffused into a bilayered stent graft retain and express a retrovirally transduced gene for 7 months in vivo. Method: SMCs harvested from dog jugular vein were retrovirally transduced to introduce genes for tissue plasminogen activator (t-PA) and β-galactosidase. These cells were then suffused into a novel dual-layered Dacron graft and cultured for 36 to 48 hours. The grafts were mounted on a Palmaz stent and balloon-expanded in the infrarenal aorta of the SMC donor dogs (n = 6). Grafts were recovered at 1, 2, 3, 4, 5, and 7 months. A control endograft suffused with SMCs transduced with only the β-galactosidase gene was placed in the dogs with grafts recovered at 2, 3, and 4 months. t-PA antigen concentration and expression were analyzed with an enzyme-linked immunosorbent assay. Results: Retained engineered SMCs (blue nuclei) were identified in the explanted grafts, neointima, and underlying aorta with X-gal staining. The t-PA antigen concentration and t-PA activity from the SMCs recovered from the grafts remained elevated for the duration of the experiment (7 months) at levels significantly higher (3.7 ± 0.2 ng/mL per 105 cells per 24 hours and 1.4 ± 0.1 IU/mL per 105 cells per 24 hours) than in control endografts (0.5 ± 0.03 ng/mL per 105 cells per 24 hours and 0.07 ± 0.00 IU/mL per 105 cells per 24 hours; P < .001). No graft stenosis was observed. Conclusion: Retrovirally engineered vascular SMCs survived the implantation trauma, repopulated each graft, migrated into the underlying aorta, and expressed the transduced genes for the 7-month duration of the experiment. This bilayered Dacron endograft model provides a platform to study direct intravascular gene therapy.",
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AU - Baxter, Bernard Timothy

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N2 - Purpose: The purpose of this study was to determine whether vascular smooth muscle cells (SMCs) suffused into a bilayered stent graft retain and express a retrovirally transduced gene for 7 months in vivo. Method: SMCs harvested from dog jugular vein were retrovirally transduced to introduce genes for tissue plasminogen activator (t-PA) and β-galactosidase. These cells were then suffused into a novel dual-layered Dacron graft and cultured for 36 to 48 hours. The grafts were mounted on a Palmaz stent and balloon-expanded in the infrarenal aorta of the SMC donor dogs (n = 6). Grafts were recovered at 1, 2, 3, 4, 5, and 7 months. A control endograft suffused with SMCs transduced with only the β-galactosidase gene was placed in the dogs with grafts recovered at 2, 3, and 4 months. t-PA antigen concentration and expression were analyzed with an enzyme-linked immunosorbent assay. Results: Retained engineered SMCs (blue nuclei) were identified in the explanted grafts, neointima, and underlying aorta with X-gal staining. The t-PA antigen concentration and t-PA activity from the SMCs recovered from the grafts remained elevated for the duration of the experiment (7 months) at levels significantly higher (3.7 ± 0.2 ng/mL per 105 cells per 24 hours and 1.4 ± 0.1 IU/mL per 105 cells per 24 hours) than in control endografts (0.5 ± 0.03 ng/mL per 105 cells per 24 hours and 0.07 ± 0.00 IU/mL per 105 cells per 24 hours; P < .001). No graft stenosis was observed. Conclusion: Retrovirally engineered vascular SMCs survived the implantation trauma, repopulated each graft, migrated into the underlying aorta, and expressed the transduced genes for the 7-month duration of the experiment. This bilayered Dacron endograft model provides a platform to study direct intravascular gene therapy.

AB - Purpose: The purpose of this study was to determine whether vascular smooth muscle cells (SMCs) suffused into a bilayered stent graft retain and express a retrovirally transduced gene for 7 months in vivo. Method: SMCs harvested from dog jugular vein were retrovirally transduced to introduce genes for tissue plasminogen activator (t-PA) and β-galactosidase. These cells were then suffused into a novel dual-layered Dacron graft and cultured for 36 to 48 hours. The grafts were mounted on a Palmaz stent and balloon-expanded in the infrarenal aorta of the SMC donor dogs (n = 6). Grafts were recovered at 1, 2, 3, 4, 5, and 7 months. A control endograft suffused with SMCs transduced with only the β-galactosidase gene was placed in the dogs with grafts recovered at 2, 3, and 4 months. t-PA antigen concentration and expression were analyzed with an enzyme-linked immunosorbent assay. Results: Retained engineered SMCs (blue nuclei) were identified in the explanted grafts, neointima, and underlying aorta with X-gal staining. The t-PA antigen concentration and t-PA activity from the SMCs recovered from the grafts remained elevated for the duration of the experiment (7 months) at levels significantly higher (3.7 ± 0.2 ng/mL per 105 cells per 24 hours and 1.4 ± 0.1 IU/mL per 105 cells per 24 hours) than in control endografts (0.5 ± 0.03 ng/mL per 105 cells per 24 hours and 0.07 ± 0.00 IU/mL per 105 cells per 24 hours; P < .001). No graft stenosis was observed. Conclusion: Retrovirally engineered vascular SMCs survived the implantation trauma, repopulated each graft, migrated into the underlying aorta, and expressed the transduced genes for the 7-month duration of the experiment. This bilayered Dacron endograft model provides a platform to study direct intravascular gene therapy.

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