Correlation between myocardial regeneration and the release of cytokines in ischemic hearth with intramyocardial implantation of cardiomyogenic mesenchymal stem cells

Abstract

[한글]

[영문]Mesenchymal stem cells (MSCs) represent a suitable source of autologous cells in cell therapy for the improvement of cardiac function, but its therapy has limitations due to the poor differentiation after cell transplantation. Recently, some reports demonstrate that paracrine factors generated from MSCs-implanted heart mediate endogenous regeneration, e.g. vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and basic fibroblast growth factor (b-FGF), which play an important role in ischemic tissues. Previously, we found cardiogenic differentiation system through protein kinase C (PKC) signal which activated by phorbol 12-myristate 13-acetate. This study was designed to investigate the correlation between myocardial regeneration and cytokine release of ischemic heart with intramyocardial implantation of cardiogenic cells (CGCs). To examine the in vivo relevance of our in vitro findings, we studied the enhanced revelation of CGCs on LAD (Left anterior descending) ligated rat hearts. In the ligation group, the area of interstitial fibrosis was significantly larger (36.0±2.5%, versus 1.0±0.6% of the normal group, p<0.05). In contrast, transplantation of CGCs significantly decreased interstitial fibrosis to 8.5±3.2% when compared to the normal group (p<0.05). TUNEL-positive cells caused by ligation were significantly reduced in the CGCs-implanted group, compared with the ligation group and the MSCs-implanted group. The apoptotic indices were 32% in the ligation group, 13% in the MSCs-implanted group, and 6% in the CGCs-implanted group. In RT-PCR analysis for gene expression of cytokine molecules, the expression levels of HGF and VEGF in the CGCs-implanted group were higher (1.61 folds (HGF) and 1.33 folds (VEGF) of the level of the ligation group, respectively) and the expression levels of inflammation cytokines, such as IL-1β, IL-6 and TNF-α, were lower (0.94 folds (IL-1β), 0.80 folds (IL-6), and 0.71 folds (TNF-α) of the level of the ligation group, respectively). In conclusion, implantation of cardiogenic cell induced from MSCs and secreted cytokines proved useful in attenuating cardiac fibrosis and regenerating myocardium after myocardial infarction.