Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: their integration with recipient myocardium.
BACKGROUND
We hypothesized that tissue-engineered contractile cardiomyocyte sheets without a scaffold would show histological and electrical integration with impaired myocardium, leading to the regeneration of infarcted myocardium.


METHODS
Neonatal rat cardiomyocytes were cultured on Poly(N-isopropylacrylamide)-grafted polystyrene dishes and detached as a square cell sheet at 20 degrees C. Two sheets were stacked to make thicker contractile cardiac sheets. In cross-section, the stacked sheets looked like homogeneous heart-like tissue. Two weeks after rats were subjected to left anterior descending (LAD) ligation, two treatments were conducted: 1) cardiomyocyte sheet implantation (T group, n=10), and 2) fibroblast sheet implantation (F group, n=10). The control group underwent no additional treatment (C group, n=10).


RESULTS
Echocardiography demonstrated that cardiac performance was significantly ameliorated in the T group 2, 4, and 8 weeks after implantation. The cardiomyocyte sheets became attached to the infarcted myocardium, showed angiogenesis, expressed connexin-43, and appeared as homogeneous tissue in the myocardium Electrophysiological experiments showed a QRS complex with one peak in the treated scar area in the T group, but two peaks, indicative of branch block, in that of the other groups. Furthermore, the threshold for pacing of the recipient heart was lower in the T group than in the other groups.


CONCLUSIONS
Cardiomyocyte sheets integrated with the impaired myocardium and improved cardiac performance in a model of ischemic myocardium. Techniques using such tissue-engineered cell sheets are introducing the promising concept of tissue cardiomyoplasty to the field of regenerative medicine.
Miyagawa
Shigeru
S
Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Sawa
Yoshiki
Y
Sakakida
Satoru
S
Taketani
Satoshi
S
Kondoh
Haruhiko
H
Memon
Imran Ahmed
IA
Imanishi
Yukiko
Y
Shimizu
Tatsuya
T
Okano
Teruo
T
Matsuda
Hikaru
H
D000818:Animals; D018421:Cardiomyoplasty / Q000379:methods*; D002450:Cell Communication / Q000502:physiology; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D004594:Electrophysiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000628:therapy*; D032342:Muscle Cells / Q000166:cytology* / Q000502:physiology*; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000628:therapy*; D051381:Rats; D016378:Tissue Transplantation