Human mesenchymal stem cells derived from amniotic membrane attenuate isoproterenol (ISO)-induced myocardial injury by targeting apoptosis

Background: Currently, stem cell therapy has been proposed as an efficient strategy to prevent or treat myocardial injuries. The current study was conducted to examine cardioprotective effects of human mesenchymal stem cells derived from amniotic membrane (hAMSCs) against isoproterenol (ISO)-induced myocardial injury and explore its potential mechanisms. Methods: The hAMSCs were injected intramyocardially in male Wistar rats 28 days after last injection of ISO (170 mg/kg body weight for 4 consecutive days). The echocardiography was performed to confirm induction of myocardial damage and cardiac function 28 days after last injection of ISO and 4 weeks hAMSCs transplantation after HF induction. The expression of apoptotic markers such as Bcl-2, Bax and P53 was evaluated using Western blotting assay. Masson's trichrome staining was used to determine fibrosis. The cytoarchitecture of myocardial wall and morphology of cells were investigated using hematoxylin and eosin (H&E) staining. Results: As compared to ISO group, hAMSCs transplantation after heart failure (HF) induction significantly blunted the increasing of cardiac dimensions and restored ejection fraction (EF) and fractional shortening (FS) parameters (p<0.05). Moreover, hAMSCs transplantation after HF induction increased the expression of antiapoptotic markers such as Bcl-2 and decreased the expression of pro-apoptotic markers such as P53 and Bax (p<0.05). As compared to ISO group, hAMSCs transplantation after HF induction markedly reduced interstitial myocardial fibrosis and contributed to maintain of normal cytoarchitecture of myocardial wall and morphology of cells. Conclusion: Collectively, the results of current study suggest that transplantation of hAMSCs confers cardioprotection by targeting ISO-induced mitochondria-dependent (intrinsic) pathway of apoptosis.