Amniotic membrane mesenchymal stem cells labeled by iron oxide nanoparticles exert cardioprotective effects against isoproterenol (ISO)-induced myocardial damage by targeting inflammatory MAPK/NF-κB pathway

Abstract

The aim of the present study is to investigate the protective effects of human amniotic membrane-derived mesenchymal stem cells (hAMSCs) labeled by superparamagnetic iron oxide nanoparticles (SPIONs) against isoproterenol (ISO)-induced myocardial injury in the presence and absence of a magnetic field. ISO was injected subcutaneously for 4 consecutive days to induce myocardial injury in male Wistar rats. The hAMSCs were incubated with 100μg/ml SPIONs and injected to rats in magnet-dependent and magnet-independent groups via the tail vein. The size and shape of nanoparticles were determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Prussian blue staining was used to determine cell uptake of nanoparticles. Myocardial fibrosis, heart function, characterization of hAMSCs, and histopathological changes were determined using Masson's trichrome, echocardiography, flow cytometry, and H&E staining, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to the expression pro-inflammatory cytokines. Immunohistochemistry assay was used to determine the expression of nuclear factor-κB (NF-κB) and the Ras/mitogen-activated protein kinase (MAPK). SPION-labeled MSCs in the presence of magnetic field significantly improved cardiac function and reduced fibrosis and tissue damage by suppressing inflammation in a NF-κB/MAPK-dependent mechanism (p< 0. 05). Collectively, our findings demonstrate that SPION-labeled MSCs in the presence of magnetic field can be a good treatment option to reduce inflammation following myocardial injury. Graphical abstract.