Development of a Novel Method for Cell Transplantation Through the Coronary Artery

Abstract

Background —Cell transplantation is a promising strategy to treat end-stage heart failure. At present, a popular method to deliver cells into the heart is direct intramuscular injection. This method, however, may not be efficient in spreading cells globally into the myocardium. We have developed a novel method for cell transplantation using intracoronary infusion. Methods and Results —An L6 rat skeletal muscle cell line expressing β-galactosidase (β-gal) was generated by gene transfection and clonal selection. These cells (10 6 in 1 mL medium) were infused into explanted rat hearts through the coronary artery, followed by heterotopic heart transplantation into the abdomen of recipients. Control hearts were infused with cell-free medium. According to β-gal activity measurements, ≈5×10 5 grafted cells per heart existed on day 3, increasing to 5×10 6 on day 28 in the cell-transplanted hearts. At day 28, discrete loci positively stained for β-gal were observed throughout the cardiac layers of both left and right coronary territories. Some of them differentiated into β-gal–positive multinucleated myotubes that aligned with the cardiac fiber axis and integrated into the native myocardium, whereas others formed colonies consisting of undifferentiated myoblasts. Connexin 43, a cardiac gap junction protein, was expressed between grafted cells and native cardiomyocytes. No reduction in cardiac function was observed in a Langendorff perfusion system. Conclusions —We have developed a unique method for efficient cell transplantation based on intracoronary infusion. This method, potentially applicable in the clinical setting during cardiac surgery, could be useful to globally supply cells to the heart.