Reversal of myocardial injury using genetically modulated human skeletal myoblasts in a rodent cryoinjured heart model☆

Abstract

We hypothesized that combination therapy using human myoblasts and VEGF165 will lead to better prognosis in a failing heart. Forty-eight female Wistar rats with cryoinjured hearts were randomized into non-treated normal (group-1, n=12), DMEM injected (group-2, n=10), myoblast-transplanted (group-3, n=12) and myoblast-hVEGF(165) (group-4, n=14). Ten days after cryoinjury, 200 microl DMEM containing 3x10(6) cells or without cells was injected into the injured myocardium. Animals were maintained on cyclosporine for 6 weeks post cell transplantation. Heart function was assessed by echocardiography. Animals were sacrificed and hearts were processed for histochemical and immunohistochemical studies. Histological examination showed survival of the donor myoblasts expressing lac-z and hVEGF165 in rat cardiac tissue. Fluorescent immunostaining for vWillebrand Factor-VIII and smooth muscle actin expression at low power microscope (x100) showed significantly higher blood vessel density in group-4 (31.25+/-1.82; 24.63+/-0.92) as compared to group-2 (13.29+/-1.0; p<0.001; 9.71+/-0.81, p<0.001) and group-3 (16.50+/-1.43, p<0.001; 14.5+/-1.34, p<0.001). Echocardiography showed that ejection fraction and fractional shortening of group-3 (93.36+/-1.52%, p=0.005; 75+/-3.75%, p=0.024) and group-4 (94.8+/-1.62%, p=0.003; 76.13+/-2.15%, p=0.011) significantly improved as compared to group-2 (81.8+/-3.3%, 55.1+/-7.18%). Myoblasts carrying of hVEGF165 are potential therapeutic transgene carriers for cardiac repair.