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Ann Thorac Surg 2007;84:134-141
© 2007 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Combined Strategy Using Myoblasts and Hepatocyte Growth Factor in Dilated Cardiomyopathic Hamsters

^a Department of Surgery, Division of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
^b Department of Molecular Therapeutics, Division of Molecular Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
^c Department of Pathology, School of Allied Health Science, Faculty of Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

Accepted for publication March 19, 2007.

^_* Address correspondence to Dr Sawa, Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan (Email: sawa{at}surg1.med.osaka-u.ac.jp).

Background: There are few reports on treating dilated cardiomyopathy (DCM) with myoblast transplantation, and these show limited efficacy. Hepatocyte growth factor has cardioprotective effects on failed myocardium. Here, we combined these two treatments and analyzed cardiac function in DCM hamsters.

Methods: Twenty-seven-week-old BIO TO-2 hamsters, which show moderate cardiac remodeling, were divided into four treatment groups: myoblast transplantation (T group, n = 24), human hepatocyte growth factor gene transfection (H group, n = 29), combined treatment (T+H group, n = 21), and medium alone (C group, n = 26).

Results: Significantly better fractional shortening was observed in the T+H group compared with the others (14.9% ± 1.0%, 11.7% ± 1.5%, 11.3% ± 1.3%, and 8.6% ± 1.1 %, in the T+H, H, T, and C groups, respectively). Immunohistochemical analysis showed alpha- and beta-sarcoglycan expression in the hearts of the H and T+H groups but not in the other groups. There was less myocardial fibrosis in the H and T+H groups than in the other two, and neovascularization in the T+H group was significantly greater than in the other groups (266 ± 24, 209 ± 27, 199 ± 36, and 96 ± 17 vessels/mm², in the T+H, H, T, and C groups, respectively). Survival was significantly prolonged in the H and T+H groups compared with the other groups.

Conclusions: Hepatocyte growth factor gene transfection and myoblast transplantation preserved the cardiac function of DCM hamsters, probably through different mechanisms, and the combined treatments preserved cardiac performance better than either treatment alone. The combined therapy is a promising strategy for treating DCM.

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