Abstract 3258: A Combined Cell Sheets With Adipose Tissue Derived Mesenchymal Stem Cells and Skeletal Myoblasts Provide Complete Myocardial Regeneration in Rat Myocardial Infarction Model
Background: Skeletal myoblasts (SMB) sheets induce myocardial regeneration in failing hearts via the paracrine system by providing large amounts of cytokines. We hypothesized whether adipose tissue derived mesenchymal stem cells (ADMSC) accelerate the paracrine system of SMB sheets and improve functional performance in a rat myocardial infarction (MI) model.
Methods and Results: SMB were isolated from male Lewis rats and ADMSC from human adult female subcutaneous fat, then cultured on temperature responsive culture dishes to obtain co-cultured cell sheets (SMB+ADMSC), myoblast-single cell sheets and ADMSC-single cell sheets. Real-time PCR was used to analyze the expression of HGF and VEGF secreted only from rat myoblasts, which revealed their expression was significantly higher in the SMB+ADMSC cell sheets than the myoblast-single cell sheets (Table⇓). Further, the protein levels of those growth factors were significantly higher in the SMB+ADMSC cell sheets than the others, as shown by ELISA analysis (Table⇓). MI was induced in female athymic rats by ligating LAD, then they were divided into the following 4 groups: M; SMB+ADMSC sheets (n=9), S; SMB sheets (n=8), A; ADMSC sheets (n=8) and sham (n=8) groups. Two weeks after LAD ligation, cell sheets were implanted to scarred myocardium. Echocardiography showed SMB+ADMSC implantation induced significant improvement of cardiac function as compared with the other groups (Table⇓). These data were supported by results of pressure-volume analysis with a conductance catheter (Table⇓). Histological examinations revealed that cell diameter and percent fibrosis decreased, while vascular density was most increased in the M group (Table⇓).
Conclusions: Our results demonstrate that ADMSC can accerelate the paracrine effect of SMB sheets, thus enhancing angiogenesis, lowering fibrosis and improving cardiac function in MI model rats. Implantation of SMB+ADMSC may be a promising strategy for the treatment of heart failure.