Effectiveness of transient immunosuppression using cyclosporine for xenomyoblast transplantation for cardiac repair

Abstract

We studied the survival of human myoblast for cellular myocardial reconstruction in a porcine model of chronic myocardial ischemia with immune tolerance using transient immunosuppression. A porcine model of chronic cardiac ischemia was created in 10 pigs (DMEM medium-injected n = 4; myoblast transplanted n = 6) by clamping ameroid ring around left circumflex coronary artery. Three weeks later, 3 × 108 human myoblasts carrying lac-z reporter gene were transplanted in multiple sites (0.25 mL each) into the left ventricular wall. Immunosuppression was achieved with 5 mg/kg cyclosporine for 6 weeks after cell transplantation. After animals were euthanized between 6 and 30 weeks after cell transplantation; the heart was removed for histological studies. Discontinuation of immunosuppression after 6 weeks of cell transplantation did not result in donor cell rejection. The lac-z-positive donor cells were detected in porcine host cardiac tissue for up to 30 weeks posttransplantation, expressing human skeletal myosin heavy chain. The results highlight the effectiveness of transient immunosuppression for myoblast transplantation for cardiac repair.