DELIVERY OF PRIMARY AUTOLOGOUS SKELETAL MYOBLASTS INTO RABBIT HEART BY CORONARY INFUSION - A POTENTIAL APPROACH TO MYOCARDIAL REPAIR

Myocardial repair after injury is limited because the adult heart cann ot regenerate. We propose using autologous skeletal muscle cells (myob lasts) as a source of reserve cells for repair of regions of damaged m yocardium. This report examines two potential methods for the transfer of cells to the myocardium: selective coronary catheterization, and m yoblast infusion or myoblast injection directly into the left ventricu lar wall. Autologous, primary rabbit skeletal myoblasts were harvested , were transduced ex vivo with adenoviruses expressing the Escherichia coli beta-galactosidase (beta-gal) gene, and were infused selectively into the coronary circulation or injected directly into the myocardia l wall. After either delivery method, beta-gal expression was detectab le at the earliest times examined (3 days) and persisted for several w eeks. The method of delivery influenced the spatial pattern of beta-ga l expression. After direct injection, a localized concentration of myo blasts that decreased with distance from the injection site was visibl e primarily in the myocardial layer of the ventricle, although occasio nal staining could be detected in other layers. After coronary infusio n, discrete punctate or linear foci of beta-gal expression were found throughout the distribution of the left coronary circulation in all ca rdiac layers. After infusion or injection, beta-gal-positive cells wer e seen in direct physical apposition to cardiocytes; interestingly, be ta-gal could be detected also in some branched cells with clear cross- striations. Autologous myoblasts survived with no obvious dysrhythmic effects despite their presence in extensive or discrete loci in the my ocardium. These observations provide the first evidence that myoblast transfer is possible by catheter-based methods, and they create the ba sis for studies to investigate the functional consequences of myoblast infusion in damaged heart.