Long-term survival of AT-1 cardiomyocyte grafts in syngeneic myocardium

Abstract

The long-term viability of cardiomyocyte grafts in the adult myocardium was tested. AT-1 cardiomyocytes, a differentiated tumor line derived from transgenic mice expressing an atrial natriuretic factor-simian virus 40 T antigen fusion gene, were grafted directly into the myocardium of syngeneic animals. Viable grafts were detected as long as 4 mo postimplantation. Thymidine uptake studies suggested that the grafted cardiomyocytes retained mitotic activity. The presence of AT-1 cardiomyocyte grafts and the associated myocardial remodeling were not accompanied 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 myocardium can serve as a stable platform for cells that have been manipulated in vitro and suggests that cardiomyocyte grafts may provide a useful means for the local delivery of recombinant molecules to the heart. The long-term survival of the AT-1 cardiomyocytes in the heart also raises the possibility that similar grafting approaches may be used to replace diseased myocardium.