Using endothelial progenitor cells for gene therapy.

Abstract

Readers of Arteriosclerosis, Thrombosis, and Vascular Biology are already well aware of the high level of interest in gene therapy as a potential means of combating cardiac and vascular disease. During the last 10 years or so there have been clear demonstrations in a variety of animal models that it is possible to modulate the progress of atherosclerotic vascular disease, restenotic arterial disease, or venous graft disease by transgenic or knockout approaches. These studies have concomitantly generated a series of experiments in which local gene therapy, predominantly using adenoviral vectors, has been used to attempt to ameliorate restenosis in grafts or after vascular injury and to enhance angiogenesis in and around areas of ischemic or infarcted tissue. The essential vision of successful human gene therapy for cardiovascular diseases remains undimmed,1 but the original enthusiastic optimism has been tempered by reality: there are significant generic problems such as inflammatory side effects due to the current generation of viral vectors and potential safety concerns for long-term gene therapy highlighted by the cases of leukemia in children being treated for immunodeficiency diseases2 in addition to the complications inherent in trying to treat complex disease processes with a single magic bullet. Nonetheless, several uncontrolled clinical trials, but very few controlled trials so far, have suggested benefit from local transfer of the gene for vascular endothelial growth factor into the heart after myocardial infarction or into the leg to overcome peripheral ischemia.3,4 See page 2266 While the significant hurdles that need to be overcome to make cardiovascular gene therapy a clinical …