NATURAL-HISTORY OF FETAL-RAT CARDIOMYOCYTES TRANSPLANTED INTO ADULT-RAT MYOCARDIAL SCAR TISSUE

Background Fetal rat cardiomyocytes transplanted into left ventricular scar tissue of the adult rat heart limit scar expansion and improve h eart function. This study determined morphologic changes of transplant ed fetal rat cardiomyocytes in myocardial scar tissue. Methods and Res ults The left ventricles of 500-g Sprague-Dawley rats were cryodamaged . At 4 weeks after myocardial injury, a transmural scar (54 +/- 11 mm( 2)) (mean +/- 1 SDak) formed at the apex (n=6). Cardiomyocytes freshly isolated from 18-day-gestation Sprague-Dawley rat hearts were transfe cted with plasmid containing the P-galactosidase and then injected int o the 4-week-old scar tissue. Cell culture medium was injected into th e scar tissue of control animals. At 4 weeks posttransplantation, the cardiomyocytes had formed cardiac tissue (20.7 +/- 6.9 mm?, n=14), whi ch stained positively for P-galactosidase activity in the scar (90.4 /- 25 mm,2 n=14). The transplanted cardiomyocytes formed sarcomeres an d were linked by junctions composed of desmosomes and fascia adherens. Lymphocyte infiltration occurred despite use of cyclosporin A. No myo cardial tissue was found in the scar tissue of the control animals (n= 14). More arterioles and venules were found (P<.01) in the cardiomyocy te grafts (1.2 +/- 0.6 vessel/0.8 mm(2); n=14) than in the control sca r tissue (0.1 +/- 0.1 vessels/0.8 mm(2); n=14). At 20 weeks post-trans plantation, the transplant tissue size (6 +/- 6 mm(2); n=7) was smalle r (P=.007 than 4-week old transplant, and the scar (162 +/- 46 mm?; n= 7) was larger (P=.005) than 4-week-old scar. Lymphocyte infiltration w as still present among the remaining transplanted cells. Conclusions T his study demonstrated that cardiac tissue formed by transplanted feta l cardiomyocytes in the myocardial scar tissue decreased in size with time probably secondary to rejection.