Impaired myocardium regeneration with skeletal cell sheets--a preclinical trial for tissue-engineered regeneration therapy.
BACKGROUND
We hypothesized that autologous skeletal cell (SC) sheets regenerate the infract myocardium in porcine heart as a preclinical trial.


RESULTS
The impaired heart was created by implantation of ameroid constrictor on left anterior descending for 4 weeks. SCs isolated from leg muscle were cultured and detached from the temperature-responsive domain-coated dishes as single monolayer cell sheet at 20 degrees C. The following therapies were conducted: SC sheets (SC group, n=5); sham (C group n=5). Echocardiography demonstrated that cardiac performance was significantly improved in the SC group 3 and 6 months after operation (fractional area shortening, 3 months; SC vs. C=49.5+/-2.8 vs. 24.6+/-2.0%, P<0.05) and left ventricle dilatation was well attenuated in the SC group. Color kinesis index showed that distressed regional diastolic and systolic function in infarcted anterior wall was significantly recovered (SC vs. C=57.4+/-8.6 vs. 30.2+/-4.7%, P<0.05, diastolic: 58.5+/-4.5 vs. 35.4+/-6.6%, P<0.05, systolic). Factor VIII immunostains demonstrated that vascular density was significantly higher in the SC group than the C group. And % fibrosis and cell diameter were significantly lower in the SC group. And hematoxylin-eosin staining depicted that skeletal origin cells and well-developed-layered smooth muscle cells were detected in the implanted area. Positron emission tomography showed better myocardial perfusion and more viable myocardial tissue in the distressed myocardium receiving SC sheets compared with the myocardium receiving no sheets.


CONCLUSIONS
SC sheet implantation improved cardiac function by attenuating the cardiac remodeling in the porcine ischemic myocardium, suggesting a promising strategy for myocardial regeneration therapy in the impaired myocardium.
Miyagawa
Shigeru
S
Division of Cardiovascular Surgery, Department of Surgery, Faculty of Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Saito
Atsuhiro
A
Sakaguchi
Taichi
T
Yoshikawa
Yasushi
Y
Yamauchi
Takashi
T
Imanishi
Yukiko
Y
Kawaguchi
Naomasa
N
Teramoto
Noboru
N
Matsuura
Nariaki
N
Iida
Hidehiro
H
Shimizu
Tatsuya
T
Okano
Teruo
T
Sawa
Yoshiki
Y
D000758:Anesthesia / Q000379:methods / Q000662:veterinary; D000818:Animals; D003971:Diastole; D048091:Guided Tissue Regeneration / Q000379:methods*; D006321:Heart / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000502:physiology / Q000637:transplantation*; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D012038:Regeneration / Q000502:physiology*; D013318:Stroke Volume; D013552:Swine; D013599:Systole / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods* / Q000639:trends; D014463:Ultrasonography