Smooth muscle cell transplantation into myocardial scar tissue improves heart function

This study was designed to evaluate the effect of smooth muscle cell transp lantation into myocardial ventricular scar formed by cryo-necrosis. The lef t ventricular free wall (LVFW) of adult rats was cryo-necrosed. At 4 weeks alter cryo-injury cultured fetal rat stomach smooth muscle cells (transplan ted group, n=10) or culture medium (control, n = 10) were transplanted. Sha m animals (n = 8) were similarly operated but without cryo-necrosis and tra nsplantation. The animals were administered a daily maintenance dose of cyc losporin A (5 mg/kg). At 8 weeks after cryo-injury, he art function was eva luated using a Langendorff preparation. Myocardial scar and transplanted ce lls were assessed histologically. Transplanted smooth muscle cells survived and formed smooth muscle cell tissue. as assessed by immunostaining agains t smooth muscle cell actin, within the myocardial scar. In the control hear ts no muscle tissue was found in the scar. Angiogenesis occur-ed (P<0.001) in the transplanted scar compared to the control scar, The transplanted cel ls increased the scar thickness (P<0.01) by hyperplasia and prevented (P<0. 001) the dilatation of the ventricular chamber size compared to the control hearts. For physiological left ventricular volumes of 0.04 to 0.28 ml, the systolic and developed pressures in the transplanted group were greater (P <0.001) than the control group, but less (P<0.001) than those of the sham g roup. Transplanted smooth muscle cells formed smooth muscle tissue in myoca rdial scar tissue and improved contractile function compared to control hea rts. (C) 1999 Academic Press.