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Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: their integration with recipient myocardium.

Abstract：

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.

journal_name

Transplantation

journal_title

Transplantation

authors

Miyagawa S,Sawa Y,Sakakida S,Taketani S,Kondoh H,Memon IA,Imanishi Y,Shimizu T,Okano T,Matsuda H

doi

10.1097/01.tp.0000181163.69108.dd

subject

Has Abstract

pub_date

2005-12-15 00:00:00

pages

1586-95

issue

eissn

0041-1337

issn

1534-6080

pii

00007890-200512150-00013

journal_volume

pub_type

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Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: their integration with recipient myocardium.