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 VEGF(165) 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-4, 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 mu l DMEM containing 3 x 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 immunohistochernical Studies. Results: Histological examination showed survival of the donor myoblasts expressing lac-z and hVEGF(165) in rat cardiac tissue. Fluorescent immunostaining for vWillebrand Factor-VIII and smooth muscle actin expression at low power microscope (x 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 +/- 0.8 1, 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. (c) 2005 European Society of Cardiology. Published by Elsevier B.V.. All rights reserved.