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Combined strategy using myoblasts and hepatocyte growth factor in dilated cardiomyopathic hamsters
Haruhiko Kondoh1, Yoshiki Sawa, Norihide Fukushima
1Department of Surgery, Division of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Insights
Combined therapy of hepatocyte growth factor gene transfection and myoblast transplantation significantly improved cardiac function in dilated cardiomyopathy (DCM) hamsters. This novel approach offers a promising strategy for treating DCM by enhancing cardiac performance.
Area of Science:
- Cardiology
- Regenerative Medicine
- Gene Therapy
Background:
- Dilated cardiomyopathy (DCM) treatment remains challenging, with limited efficacy reported for myoblast transplantation.
- Hepatocyte growth factor (HGF) demonstrates cardioprotective properties in myocardial conditions.
Purpose of the Study:
- To investigate the combined effects of myoblast transplantation and HGF gene transfection on cardiac function in DCM hamsters.
- To evaluate the efficacy of this combined therapy compared to individual treatments.
Main Methods:
- BIO TO-2 hamsters with moderate cardiac remodeling were assigned to four groups: myoblast transplantation (T), HGF gene transfection (H), combined treatment (T+H), and control (C).
- Cardiac function was assessed, and immunohistochemical analysis was performed to evaluate sarcoglycan expression, fibrosis, and neovascularization.
Main Results:
- The combined T+H group exhibited significantly improved fractional shortening (14.9%) compared to T (11.3%), H (11.7%), and C (8.6%) groups.
- Alpha- and beta-sarcoglycan expression, reduced fibrosis, and increased neovascularization (266 vessels/mm²) were observed in the T+H group.
- Survival rates were significantly prolonged in both H and T+H groups compared to T and C groups.
Conclusions:
- Combined HGF gene transfection and myoblast transplantation effectively preserved cardiac function in DCM hamsters.
- The synergistic effect of combined therapy outperformed individual treatments, suggesting distinct underlying mechanisms.
- This combined therapeutic strategy presents a promising avenue for managing dilated cardiomyopathy.
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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