Development of a novel method for cell transplantation through the coronary artery

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 effici ent in spreading cells globally into the myocardium. We have developed a no vel method for cell transplantation using intracoronary infusion. Methods ann Results-An L6 rat skeletal muscle cell line expressing beta -ga lactosidase (beta -gal) was generated by gene transfection and clonal selec tion. These cells (10(6) in 1 mL medium) were infused into explanted rat he arts through the coronary artery, followed by heterotopic heart transplanta tion into the abdomen of recipients. Control hearts were infused with cell- free medium. According to beta -gal activity measurements, approximate to 5 x10(5) grafted cells per heart existed on day 3, increasing to 5X10(6) on d ay 28 in the cell-transplanted hearts. At day 28, discrete loci positively stained for beta -gal were observed throughout the cardiac layers of both l eft and right coronary territories. Some of them differentiated into beta - gal-positive multinucleated myotubes that aligned with the cardiac fiber ax is and integrated into the native myocardium, whereas others formed colonie s consisting of undifferentiated myoblasts. Connexin 43, a cardiac gap junc tion 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 transplant ation 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.