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J Thorac Cardiovasc Surg 2006;132:918-924
© 2006 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Grafted skeletal myoblast sheets attenuate myocardial remodeling in pacing-induced canine heart failure model

^a Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
^b Department of Molecular Pathology, School of Allied Health Science, Osaka University Graduate School of Medicine, Osaka, Japan
^c Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.

Received for publication October 23, 2005; revisions received December 19, 2005; accepted for publication January 10, 2006.

^_* Address for reprints: Yoshiki Sawa, MD, PhD, Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine (E1), 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. (Email: sawa{at}surg1.med.osaka-u.ac.jp).

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 1.52.5 x 10⁶ 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.