Novel Mesenchymal Stem Cell Strategy in Alleviating Toll-Like Receptor-4, p53 and Nrf2 Signaling in Isoproterenol-Induced Myocardial Infarction in Rat Model

Mesenchymal stem cells (MSCs) are multipotent stromal cells that merit the differentiation into various cell types. The present study was designed to test the hypothesis that the cardioprotective effect of MSCs transplantation and digoxin treatment is mediated via the regulation of messenger RNA gene expression of pro-inflammatory cytokines and apoptotic markers. Myocardial infarction was induced in Wistar rats via isoproterenol injection in a dose of (85 mg/kg, subcutaneously, twice at an interval of 24 h). Four weeks post-MSCs transplantation and digoxin treatment a significant reduction in serum cardiac markers, aspartate aminotransferase, creatine kinase-MB and troponine II was observed. Meanwhile, isoproterenol significantly reduced the gene and protein expression of the oxidative stress marker nuclear-related factor-2 (Nrf2) with a concomitant elevation in (MDA) level and inflammatory markers toll-like receptor-4 (TLR-4), intercellular adhesion molecules (ICAMs) and (VCAM-1). Moreover, apoptotic marker (P53) was significantly down-regulated. This was confirmed by histopathological investigations. It was hypothesized that MSCs transplantation was superior over digoxin treatment regimen in improving heart function.