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Fetal rat cardiomyocytes transplanted into left ventricular scar tissue of the adult rat heart limit scar expansion and improve heart function. This study determined morphologic changes of transplanted fetal rat cardiomyocytes in myocardial scar tissue.The left ventricles of 500-g Sprague-Dawley rats were cryodamaged. At 4 weeks after myocardial injury, a transmural scar (54+/-11 mm2) (mean+/-1 SDak) formed at the apex (n=6). Cardiomyocytes freshly isolated from 18-day-gestation Sprague-Dawley rat hearts were transfected with plasmid containing the beta-galactosidase and then injected into the 4-week-old scar tissue. Cell culture medium was injected into the scar tissue of control animals. At 4 weeks posttransplantation, the cardiomyocytes had formed cardiac tissue (20.7+/-6.9 mm2, n=14), which stained positively for beta-galactosidase activity in the scar (90.4+/-25 mm2, n=14). The transplanted cardiomyocytes formed sarcomeres and were linked by junctions composed of desmosomes and fascia adherens. Lymphocyte infiltration occurred despite use of cyclosporin A. No myocardial tissue was found in the scar tissue of the control animals (n=14). More arterioles and venules were found (P.01) in the cardiomyocyte grafts (1.2+/-0.6 vessel/0.8 mm2; n=14) than in the control scar tissue (0.1+/-0.1 vessels/0.8 mm2; n=14). At 20 weeks post-transplantation, the transplant tissue size (6+/-6 mm2; n=7) was smaller (P=.007) than 4-week old transplant, and the scar (162+/-46 mm2; n=7) was larger (P=.005) than 4-week-old scar. Lymphocyte infiltration was still present among the remaining transplanted cells.This study demonstrated that cardiac tissue formed by transplanted fetal cardiomyocytes in the myocardial scar tissue decreased in size with time probably secondary to rejection.