Combined Application of Human Amniotic Membrane Mesenchymal Stem Cells and a Modified PGS-co-PCL Film in an Experimental Model of Myocardial Ischemia-Reperfusion Injury.

Abstract

According to the World Health Organization (WHO), about 3.9 million people die annually of ischemic heart disease (IHD). Several clinical trials have shown that stem cell therapy is a promising therapeutic approach to IHD. Human amniotic membrane mesenchymal stem cells (hAMSCs) positively affect the repair of myocardial ischemia-reperfusion (MI/R) injury by stimulating endogenous repair mechanisms. The differentiated hAMSCs with and without modified PGS-co-PCL film were applied in the myocardium. MI/R injury was induced by ligating the left anterior descending artery in 48 male Wistar rats. The rats were divided into four groups, (n = 12) animals: heart failure (HF) as the control group, HF + MSCs, HF + MSCs + film, and HF + film. Echocardiography was performed 2 and 4weeks after MI/R injury moreover the expression of the VEGF protein was assessed in the rat heart tissue via immunohistochemistry. In vitro, our result shows fantastic cell survival when seeded on film. In vivo, the left ventricle ejection fraction (LEVD), fractional shortening (FS), end-diastolic (EDV), and stroke volume (SV) have been increased and systolic volumes decreased in all treatment groups in comparison with control. Although combination therapy has a more positive effect on hemodynamic parameters, there is no significant difference between HF + MSCs + film with other treatment groups. Also, In the IHC assay, expression of the VEGF protein significantly increased in all intervention groups. The implantation of MSCs and the modified film significantly enhanced the cardiac functional outcome; in this regard, enhancement in cell survival and VEGF expression are involved as underlying mechanisms in which cardiac film and MSCs exert a beneficial effect.