Document Detail


Ex vivo gene therapy with adenovirus-mediated transforming growth factor beta1 expression for endovascular treatment of aneurysm: results in a canine bilateral aneurysm model.
MedLine Citation:
PMID:  12947279     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Endovascular treatment of cerebral aneurysm is safe and effective, but recurrence of disease is frequent compared with results with surgery. The purpose of this study was to determine the effects of recombinant transforming growth factor beta(1) (rTGFbeta(1)) secreted by transplanted autologous vascular smooth muscle cells (VSMC) on results of endovascular treatment.
METHODS: VSMC from canine femoral arteries were infected with adenovirus vector encoding rTGFbeta(1)/green fluorescent protein (rTGFbeta(1)/GFP) or GFP only. rTGFbeta(1) production was measured with an enzyme-linked immunosorbent assay, and autocrine and paracrine effects of rTGFbeta(1) on cell functions were quantified with a proliferation assay and collagen synthesis. A bilateral carotid aneurysm model was used to compare angiographic and pathologic results after embolization with sponges seeded (n = 14) or not seeded (n = 34) with VSMC expressing TGFbeta(1) or GFP (n = 7 each). Transgene retention was confirmed with Western blot analysis.
RESULTS: In vitro, TGFbeta(1) production varied from 0.9 to 180 ng/mL/d with increasing multiplicity of infection (MOI). Collagen synthesis was doubled at low (<300) MOI and increased by one and a half times at high (>or=300) MOI. rTGFbeta(1) was biologically active, as shown with the mink lung epithelial cell proliferation assay. VSMC grafts showed effective GFP expression up to 3 weeks after transplantation. Angiographic results were improved and neointima thickness was increased with cellular grafts, as compared with controls, but there was no significant difference between aneurysms treated with VSMC encoding rTGFbeta(1)/GFP or GFP vectors.
CONCLUSION: Cellular grafts can promote healing of aneurysms, but overexpression of rTGFbeta(1)/GFP did not demonstrate added benefits in this model.
Authors:
Edith Ribourtout; Anne-Cécile Desfaits; Igor Salazkin; Jean Raymond
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of vascular surgery     Volume:  38     ISSN:  0741-5214     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-08-29     Completed Date:  2003-09-25     Revised Date:  2012-10-03    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  576-83     Citation Subset:  IM    
Affiliation:
Research Center, Centre Hospitalaire de l'Université, de Montréal, Notre-Dame Hospital, Montreal, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae
Aneurysm / pathology,  therapy*
Angiography
Animals
Blotting, Western
Carotid Arteries*
Disease Models, Animal
Dogs
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation
Gene Therapy / methods*
Gene Transfer Techniques
Genetic Vectors
Immunohistochemistry
Muscle, Smooth, Vascular / cytology,  transplantation*
Risk Factors
Sensitivity and Specificity
Transforming Growth Factor beta / genetics,  pharmacology
Transforming Growth Factor beta1
Chemical
Reg. No./Substance:
0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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