Silica‐coated magnetic nanoparticles labeled endothelial progenitor cells alleviate ischemic myocardial injury and improve long‐term cardiac function with magnetic field guidance in rats with myocardial infarction

Abstract

Low retention of endothelial progenitor cells (EPCs) in the infarct area has been suggested to be responsible for the poor clinical efficacy of EPC therapy for myocardial infarction (MI). This study aimed to evaluate whether magnetized EPCs guided through an external magnetic field could augment the aggregation of EPCs in an ischemia area, thereby enhancing therapeutic efficacy. EPCs from male rats were isolated and labeled with silica‐coated magnetic iron oxide nanoparticles to form magnetized EPCs. Then, the proliferation, migration, vascularization, and cytophenotypic markers of magnetized EPCs were analyzed. Afterward, the magnetized EPCs (1 × 10 6 ) were transplanted into a female rat model of MI via the tail vein at 7 days after MI with or without the guidance of an external magnet above the infarct area. Cardiac function, myocardial fibrosis, and the apoptosis of cardiomyocytes were observed at 4 weeks after treatment. In addition, EPC retention and the angiogenesis of ischemic myocardium were evaluated. Labeling with magnetic nanoparticles exhibited minimal influence to the biological functions of EPCs. The transplantation of magnetized EPCs guided by an external magnet significantly improved the cardiac function, decreased infarction size, and reduced myocardial apoptosis in MI rats. Moreover, enhanced aggregations of magnetized EPCs in the infarcted border zone were observed in rats with external magnet‐guided transplantation, accompanied by the significantly increased density of microvessels and upregulated the expression of proangiogenic factors, when compared with non‐external‐magnet‐guided rats. The magnetic field‐guided transplantation of magnetized EPCs was associated with the enhanced aggregation of EPCs in the infarcted border zone, thereby improving the therapeutic efficacy of MI.

LncRNA H19 ameliorates myocardial infarction‐induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A

“…However, the potential role of H19 in AMI is still far from clear. Inflammation and apoptosis are two crucial factors that contribute to AMI and the subsequent cardiac remoulding . Interestingly, investigators have verified that H19 is a key mediator involved in myocardial inflammatory reactions and apoptosis .…”

“…The rat AMI model was established as previously described . Briefly, animals were anaesthetized with intraperitoneally injected pentobarbital sodium (60 mg/kg).…”

“…The apoptosis index (AI) was calculated as the ratio of TUNEL‐positive cells (red) to total cardiomyocytes (blue). Myocardial remodelling after infarction was determined by Masson's staining as previously described . Areas stained in blue indicate the deposition of collagen fibrils.…”

“…Quantitative RT-PCR (qRT-PCR) was performed as previously described. 19 The primer sequences for the real- For the Western blot assay, myocardial samples were lysed and proteins were extracted according to the specification of manufacturers. Total proteins were separated by 10% SDS-PAGE and electrophoretically transferred onto polyvinylidene fluoride (PVDF) membranes (Millipore).…”

“…The rat AMI model was established as previously described. 19 Briefly, animals were anaesthetized with intraperitoneally injected pentobarbital sodium (60 mg/kg). Then, a volume-controlled small animal respirator was used to support the breathing of the rats through a tracheal cannula, and a standard electrocardiogram was used to continuously monitor the heart rate.…”