Catheter-based stem cell and gene therapy for refractory myocardial ischemia

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Abstract
Intramyocardial delivery of genes and cells derived from bone marrow has been evaluated in several small studies of 'no-option' symptomatic patients with chronic ischemic coronary artery disease. Clinical experience with intramyocardial gene delivery is limited to genes encoding isoforms of vascular endothelial cell growth factor. In the largest study (Euroinject One), 80 patients were randomized to receive a plasmid encoding vascular endothelial cell growth factor 165 or placebo. The results of this study suggested no beneficial therapeutic effect of this strategy. The experience with stem cells is limited to use of autologous, nonexpanded, nonmanipulated bone-marrow-derived cells; thus, the number of injected stem cells reflects their natural proportion within the bone marrow. The results of these preliminary studies suggest this approach is feasible and has a high safety profile. Although no conclusion can yet be made regarding efficacy, the improved myocardial perfusion in all four studies described in this Review is encouraging. Data from assessments of individual patients, however, suggests a wide variability in response, underscoring the need for further bench and clinical investigations.

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