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

Abstract

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-hVEGF165 (group-4, n = 14). Ten days after cryoinjury, 200 μl DMEM containing 3 × 106 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 (× 100) 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. © 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.