Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Drug Deliv Transl Res. 2021 Feb;11(1):242-254. doi: 10.1007/s13346-020-00788-3.
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 100 μg/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.
本研究旨在探讨超顺磁性氧化铁纳米粒子（SPIONs）标记的人羊膜间充质干细胞（hAMSCs）在磁场存在和不存在的情况下对异丙肾上腺素（ISO）诱导的心肌损伤的保护作用。通过皮下注射 ISO 连续 4 天诱导雄性 Wistar 大鼠心肌损伤。将 hAMSCs 与 100μg/ml SPIONs 孵育，并通过尾静脉将其注入磁场依赖组和磁场非依赖组的大鼠体内。通过动态光散射（DLS）和透射电子显微镜（TEM）测定纳米颗粒的大小和形状。普鲁士蓝染色用于确定细胞对纳米颗粒的摄取。使用马松三色染色、超声心动图、流式细胞术和 H&E 染色分别测定心肌纤维化、心脏功能、hAMSCs 特征和组织病理学变化。酶联免疫吸附测定（ELISA）用于测定促炎细胞因子的表达。免疫组织化学检测用于测定核因子-κB（NF-κB）和 Ras/丝裂原活化蛋白激酶（MAPK）的表达。磁场中 SPION 标记的 MSC 可通过抑制炎症反应（NF-κB/MAPK 依赖性机制）显著改善心脏功能，减少纤维化和组织损伤（p<0.05）。综上所述，我们的研究结果表明，磁场中 SPION 标记的 MSC 可能是一种减少心肌损伤后炎症的良好治疗选择。示意图。
