Combined strategy using myoblasts and hepatocyte growth factor in dilated cardiomyopathic hamsters.
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.
Kondoh
Haruhiko
H
Department of Surgery, Division of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Sawa
Yoshiki
Y
Fukushima
Norihide
N
Matsumiya
Goro
G
Miyagawa
Shigeru
S
Kitagawa-Sakakida
Satoru
S
Imanishi
Yukiko
Y
Kawaguchi
Naomasa
N
Matsuura
Nariaki
N
Matsuda
Hikaru
H
D000818:Animals; D001835:Body Weight; D002311:Cardiomyopathy, Dilated / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006224:Cricetinae; D004452:Echocardiography; D015316:Genetic Therapy; D006339:Heart Rate; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D008017:Life Expectancy; D008297:Male; D032446:Myoblasts / Q000637:transplantation*; D009206:Myocardium / Q000473:pathology
C066855:HGF protein, human; D017228:Hepatocyte Growth Factor