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Chapter 8: CARDIOVASCULAR TISSUE MODIFICATION BY GENETIC APPROACHES CELLULAR TRANSPLANTATION

The implantation of cells expressing recombinant genes into the heart or vasculature is termed ex vivo gene transfer. Nabel et al.3 demonstrated a cell-based vascular gene-transfer technique. By reimplanting endothelial cells transfected ex vivo with a retroviral P-galactosidase vector on the surface of balloon-injured porcine iliofemoral arteries, genetically modified cells could be detected up to 2 to 4 weeks following reimplantation. Wilson et al.5 demonstrated expression of a reporter gene from endothelial cells implanted on a Dacron graft and placed in the carotid arteries of dogs. In addition to endothelial cells, ex vivo-transfected smooth muscle cells have been introduced in the vasculature.46 Lynch et al.47 reported the seeding of smooth muscle cells transfected with the adenosine deaminase gene into endothelium-denuded blood vessels. Another application of ex vivo gene transfer is the engineering of vascular grafts seeded with endothelial cells previously transfected in a culture dish.48 Seeding of vascular grafts with soluble vascular cell adhesion molecules (sVCAMs) (see Chap. 5) using adenoviral ex vivo gene transfer was reported by Chen et al.49

Implantation of genetically modified myoblasts or fibroblasts into skeletal muscle is an attractive gene-transfer method because the gene product can be delivered systemically. Indeed, several investigators have reported successful gene delivery using these approaches.50-52 In a mouse model, myoblasts were transplanted and supported sustained delivery of functionally active erythropoietin to correct anemia associated with renal failure.53 The myoblast method potentially could provide an approach for the delivery of insulin (diabetes), atrial natriuretic peptide (hypertension or heart failure), or apolipoprotein AI (atherosclerosis).

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