Grafted skeletal myoblast sheets attenuate myocardial remodeling in pacing-induced canine heart failure model.
OBJECTIVE
To overcome problems related to the intramyocardial injection of cells, including cell loss and a limited graft area, we developed a cell delivery system that uses tissue-engineered myoblast grafts grown as sheets. Here, we assessed the feasibility and efficacy of our method in a canine dilated cardiomyopathy model.


METHODS
Skeletal myoblasts were incubated on temperature-responsive culture dishes, and the sheets of cells were detached by decreasing the temperature. Twelve dogs were given continuous ventricular pacing at 230 beats/min for 4 weeks; then the myoblast sheets (n = 5) were grafted onto the left ventricular wall or a sham operation was performed (n = 7). The number of cells was adjusted to 1.5 approximately 2.5 x 10(6) cells per graft, and each dog received approximately 20 grafts.


RESULTS
The cell sheets were easily grafted onto a large area of the left ventricular surface, and there were no serious sequelae. Four weeks after graft implantation, echocardiography demonstrated that the left ventricular ejection fraction (graft, 26.0% +/- 5.6%; control, 19.5% +/- 6.8%; P < .05) and fractional shortening (graft, 17.9% +/- 3.6%; control, 7.8% +/- 2.1%; P < .05) were significantly ameliorated with reduced left ventricular dilatation (graft, 7.3 +/- 1.3 cm2; control, 10.2 +/- 0.4 cm2; P < .05) and increased wall thickness (graft, 5.6 +/- 0.7 mm; control, 4.4 +/- 0.6 mm; P < .05). Histologic evidence indicated the grafted myoblasts had survived, accompanied by a significant reduction in fibrosis and apoptosis, and a significant increase in proliferation.


CONCLUSIONS
Grafting of skeletal myoblast sheets attenuated cardiac remodeling and improved cardiac performance. This novel method was feasible and effective in a large animal model, suggesting an innovative and promising strategy for treating patients with end-stage dilated cardiomyopathy.
Hata
Hiroki
H
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Suita, Japan.
Matsumiya
Goro
G
Miyagawa
Shigeru
S
Kondoh
Haruhiko
H
Kawaguchi
Naomasa
N
Matsuura
Nariaki
N
Shimizu
Tatsuya
T
Okano
Teruo
T
Matsuda
Hikaru
H
Sawa
Yoshiki
Y
D000818:Animals; D002304:Cardiac Pacing, Artificial; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology* / Q000601:surgery*; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D020257:Ventricular Remodeling