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Somatostatin gene transfer and expression in endothelial cells
R Sarkar1, S Finniss, C J Dickinson
1Department of Surgery, University of Michigan Medical Center, Ann Arbor, USA.
Journal of Vascular Surgery
|June 10, 1998
Summary
Retroviral gene transfer successfully enabled canine endothelial cells to produce biologically active somatostatin. This gene therapy approach shows promise for localized somatostatin delivery in vascular beds, though species-specific differences were observed.
Area of Science:
- Vascular Biology
- Gene Therapy
- Endocrinology
Background:
- Somatostatin exhibits antiproliferative and antisecretory effects with potential clinical applications.
- Retroviral gene transfer offers a method for localized delivery of somatostatin to specific vascular beds via endothelial cells (ECs).
Purpose of the Study:
- To determine if endothelial cells transduced with somatostatin gene could produce and process the peptide.
- Investigate the feasibility of using retroviral gene transfer for local somatostatin delivery to vascular tissues.
Main Methods:
- Cultured canine venous, rat aortic, and rat microvascular ECs were transfected with retroviruses encoding human somatostatin cDNA or beta-galactosidase.
- Analysis included total and isoform somatostatin production, beta-galactosidase expression uniformity, and effects on EC proliferation.
Main Results:
- Canine ECs transduced with somatostatin gene produced significantly higher levels of somatostatin compared to controls.
- Somatostatin-14 was the predominant isoform produced, with stable production across passages and no adverse effects on canine EC growth.
- Rat ECs failed to produce somatostatin, likely due to promoter silencing affecting transgene expression.
Conclusions:
- Retroviral gene transfer to canine ECs yields physiologically relevant concentrations of active somatostatin.
- Species-specific differences in EC somatostatin production exist, with promoter silencing a potential barrier to gene expression.
- This gene therapy strategy may enable targeted somatostatin delivery to specific vascular regions.