Abstract
BackgroundWe examined whether a vascular smooth muscle cell (SMC) sheet is effective in the treatment of a rat myocardial infarction (MI) model.MethodsWe examined the effect of SMC sheet on the cardiac function and cardiac remodeling in a rat MI model in comparison with their effect of dermal fibroblast (DFB) sheet in vivo. Furthermore, we estimated the apoptosis and secretion of angiogenic factor of SMC under hypoxic condition in comparison with DFB. Seven days after MI, monolayer cell sheets were transplanted on the infarcted area (SMC transplantation group, SMC-Tx; DFB transplantation group, DFB-Tx; no cell sheet transplantation group, Untreated; neither MI nor cell sheet transplantation group, Sham). We evaluated cardiac function by echocardiogram, degree of cardiac remodeling by histological examination, and secretion of angiogenic growth factor by enzyme immunoassay.ResultsTwenty-eight days after transplantation, SMC-Tx showed the following characteristics compared with the other groups: 1) significantly greater fractional area shortening (SMC-Tx, 32.3 ± 2.1 %; DFB-Tx, 23.3 ± 2.1 %; untreated, 25.1 ± 2.6 %), 2) suppressed left ventricular dilation, smaller scar expansion, and preserved wall thickness of the area at risk and the posterior wall, 3) decreased fibrosis, preserved myocardium in the scar area, and greater number of arterioles in border-zone, 4) tight attachment of SMC sheets on the scarred myocardium, and less apoptotic cell death. In in vitro experiments, SMCs secreted higher amounts of basic fibroblast growth factor (SMC, 157.7 ± 6.4 pg/ml; DFB, 3.1 ± 1.0 pg/ml), and showed less apoptotic cell death under hypoxia.ConclusionsOur results illustrate that transplantation of SMC sheets inhibited the progression of cardiac remodeling and improve cardiac function. These beneficial effects may be due to superior SMC survival.
Highlights
We examined whether a vascular smooth muscle cell (SMC) sheet is effective in the treatment of a rat myocardial infarction (MI) model
We examined the effect of SMC sheet on the cardiac function and cardiac remodeling in a rat MI model in comparison with their effect of dermal fibroblast (DFB) sheet in vivo
Cardiac function: echocardiography The final cell counts for monolayered SMCs and DFBs before transplantation were 3.1 ± 0.2 × 106 and 1.5 ± 0.9 × 106 cells, respectively (n = 6 each)
Summary
We examined whether a vascular smooth muscle cell (SMC) sheet is effective in the treatment of a rat myocardial infarction (MI) model. Cell transplantation using several cell sources can prevent cardiac dysfunction after MI and dilated cardiomyopathy (DCM) in animal models and in clinical trials: bone marrow mononuclear cells [1], mesenchymal stem cells [2] and skeletal myoblasts [3]. Cell sheet technology has been developed using temperature-responsive culture dishes Using this method, cells are harvested from dishes by a simple temperature reduction [6]. Skeletal myoblast and adipose-tissue derived mesenchymal stem cell sheets attenuate cardiac remodeling in rat MI models [8, 9]. We examine whether a SMC sheet is effective in the prevention of cardiac dysfunction and remodeling in a rat MI model
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