IN-VIVO SURVIVAL AND FUNCTION OF TRANSPLANTED RAT CARDIOMYOCYTES

Recent studies have demonstrated the feasibility of transplanting feta l mouse cardiomyocytes into the hearts of adult syngeneic mice. Howeve r, the function of the transplanted cardiomyocytes and their capacity to survive in fibrous connective tissue were not assessed. In the pres ent study, we evaluated the viability and contractility of transplante d fetal and neonatal rat cardiomyocytes in the connective tissue of th e adult rat hindlimb. Purified fetal or neonatal rat cardiomyocytes we re cultured. These cells contained sarcomeres, formed junctions compos ed of desmosomes and fascia adherens, and contracted regularly and spo ntaneously. A fetal or neonatal cardiomyocyte suspension was injected into the subcutaneous tissue of adult rat hindlimbs. Cyclosporin A (5 mg/kg) was administered subcutaneously daily for the 3-month duration of the study, at which rime the animals were killed. The transplanted cardiomyocytes formed 'tissue' in vivo that increased in size for the first 2 weeks and remained the same size at the third week. The tissue derived from the transplanted fetal cardiomyocytes contracted spontan eously at a rate of 73+/-12 bpm, and that from the neonatal cardiomyoc ytes contracted at a rate of 43+/-21 bpm. The electrocardiogram was si milar to that seen in myocardium with an idioventricular rhythm. Histo logically, the tissue appeared to be cardiac muscle with sarcomeres. A ngiogenesis occurred in the cardiomyocyte graft. In summary, a cell su spension of cultured fetal and neonatal rat cardiomyocytes transplante d into the adult rat hindlimb formed contractile cardiac tissue in the subcutaneous connective tissue.