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

Background: We hypothesized that combination therapy using human myoblasts and VEGF165 will lead to better prognosis in a failing heart.

Methods: 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.

Results: 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%).

Conclusion: Myoblasts carrying of hVEGF165 are potential therapeutic transgene carriers for cardiac repair.