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Targeted mitigation of neointimal hyperplasia via magnetic field-directed localization of superparamagnetic iron oxide nanoparticle-labeled endothelial progenitor cells following carotid balloon catheter injury in rats - 23/07/24

Doi : 10.1016/j.biopha.2024.117022 
Zhongxuan Li a, b, 1, Yingqian Zhang a, 1, Mingrui Ma b, Wei Wang a, Hui Hui c, d, e, h, , Jie Tian c, d, f, g, h, , Yundai Chen a,
a Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing 100048, China 
b Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing 100853, China 
c CAS Key Laboratory of Molecular Imaging, Institute of Automation, Beijing 100190, China 
d Beijing Key Laboratory of Molecular Imaging, Beijing 100190, China 
e University of Chinese Academy of Sciences, Beijing 100080, China 
f School of Engineering Medicine & School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China 
g Key Laboratory of Big Data-Based Precision Medicine (Beihang University), Ministry of Industry and Information Technology of China, Beijing 100191, China 
h National Key Laboratory of Kidney Diseases, Beijing 100853, China 

Corresponding authors at: CAS Key Laboratory of Molecular Imaging, Institute of Automation, Beijing 100190, China.CAS Key Laboratory of Molecular Imaging, Institute of AutomationBeijing100190China⁎⁎Corresponding author.

Abstract

Background

The transplantation of endothelial progenitor cells (EPCs) has been shown to reduce neointimal hyperplasia following arterial injury. However, the efficacy of this approach is hampered by limited homing of EPCs to the injury site. Additionally, the in vivo recruitment and metabolic activity of transplanted EPCs have not been continuously monitored.

Methods

EPCs were labeled with indocyanine green (ICG)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) and subjected to external magnetic field targeting to enhance their delivery to a carotid balloon injury (BI) model in Sprague–Dawley rats. Magnetic particle imaging (MPI)/ fluorescence imaging (FLI) multimodal in vivo imaging, 3D MPI/CT imaging and MPI/FLI ex vivo imaging was performed after injury. Carotid arteries were collected and analyzed for pathology and immunofluorescence staining. The paracrine effects were analyzed by enzyme-linked immunosorbent assay.

Results

The application of a magnetic field significantly enhanced the localization and retention of SPIONs@PEG-ICG-EPCs at the site of arterial injury, as evidenced by both in vivo continuous monitoring and ex vivo by observation. This targeted delivery approach effectively inhibited neointimal hyperplasia and increased the presence of CD31-positive cells at the injury site. Moreover, serum levels of SDF-1α, VEGF, IGF-1, and TGF-β1 were significantly elevated, indicating enhanced paracrine activity.

Conclusions

Our findings demonstrate that external magnetic field-directed delivery of SPIONs@PEG-ICG-EPCs to areas of arterial injury can significantly enhance their therapeutic efficacy. This enhancement is likely mediated through increased paracrine signaling. These results underscore the potential of magnetically guided SPIONs@PEG-ICG-EPCs delivery as a promising strategy for treating arterial injuries.

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Graphical Abstract




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Highlights

External magnetic fields guided SPIONs@PEG-ICG-EPCs to damaged arteries.
Transplantation of SPIONs@PEG-ICG-EPCs reduced neointimal hyperplasia.
EPCs show potential in reducing neointimal hyperplasia following vascular injury.

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Abbreviations : EPCs, SPIONs, CAD, PCI, BI, DESs, ISR, ECs, MPI, FLI, SDF-1a, VEGF, TGF-β1, IGF-1, ECFCs, FITC-UEA-1, Dil-ac-LDL, HUVECs, TEM

Keywords : Endothelial progenitor cells, Magnetic targeting, SPIONs, Neointimal hyperplasia, Magnetic particle imaging


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