MRI tracing of ultrasmall superparamagnetic iron oxide nanoparticle-labeled endothelial progenitor cells for repairing atherosclerotic vessels in rabbits

摘要

Endothelial progenitor cells (EPCs) have been discovered to be relevant to the prognosis of cardiovascular diseases. Previous research has demonstrated that EPCs serve vital roles in the occurrence and development of atherosclerosis. Significant improvements have been made in MRI technology and in the experimental use of EPCs for therapeutic angiogenesis and vascular repair. Nevertheless, the migratory, adhesive, proliferative and angiogenic properties of EPCs remain unknown. The aims of the present study were to investigate the potential of using non-invasive monitoring with ultrasmall superparamagnetic iron oxide nanoparticle (USPION)-labeled endothelial progenitor cells (EPCs) after transplantation, and to assess the treatment outcomes in an atherosclerotic rabbit model. EPCs derived from rabbit peripheral blood samples were labeled with USPION-poly-l-lysine (USPION-PLL). The morphology, proliferation, adhesive ability and labeling efficiency of the EPCs were determined by optical and electron microscopy. Moreover, biological activity was assessed by flow cytometry. In addition, T2-weighted image fast spin-echo MRI was used to detect cell labeling. USPION content in the labeled EPCs was determined by Prussian blue staining and scanning electron microscopy. Rabbit atherosclerosis model was established using a high-fat diet. USPION-labeled EPCs were transplanted into rabbits, and MRI was performed 1 and 7 days after transplantation. It was found that EPCs cultured on Matrigel formed capillary-like structures, and expressed the surface markers CD133, CD31, CD34 and vascular endothelial growth factor receptor 2 (VEGFR2). The optimal USPION concentration was 32 µg/ml, as determined by adhesion and proliferation assays. It was identified that USPION-PLL nanoparticles were 10–20 nm in diameter. Histopathological analysis results indicated that 1 day after transplantation of the labeled EPCs, blue-stained granules were observed in the intima of vascular lesions in rabbit models after Prussian blue staining. Therefore, the present results suggest that USPION-labeled EPCs may play a role in repairing endothelial injury and preventing atherosclerosis .