LONG-TERM SURVIVAL OF AT-1 CARDIOMYOCYTE GRAFTS IN SYNGENEIC MYOCARDIUM

The long-term viability of cardiomyocyte grafts in the adult myocardiu m was tested. AT-1 cardiomyocytes, a differentiated tumor line derived from transgenic mice expressing an atrial natriuretic factor-simian v irus 40 T antigen fusion gene, were grafted directly into the myocardi um of syngeneic animals. Viable grafts were detected as long as 4 mo p ostimplantation. Thymidine uptake studies suggested that the grafted c ardiomyocytes retained mitotic activity. The presence of AT-1 cardiomy ocyte grafts and the associated myocardial remodeling were not accompa nied by overt cardiac arrhythmia. Electron microscopic analyses showed that the majority of the grafts were juxtaposed directly to the host myocardium and were not encapsulated. This study indicates that the my ocardium can serve as a stable platform for cells that have been manip ulated in vitro and suggests that cardiomyocyte grafts may provide a u seful means for the local delivery of recombinant molecules to the hea rt. The long-term survival of the AT-1 cardiomyocytes in the heart als o raises the possibility that similar grafting approaches may be used to replace diseased myocardium.