Can Magnetic Targeting of Magnetically Labeled Circulating Cells Optimize Intramyocardial Cell Retention?

Abstract

Therapeutic intracavitary stem cell infusion currently suffers from poor myocardial homing. We examined whether cardiac cell retention could be enhanced by magnetic targeting of endothelial progenitor cells (EPCs) loaded with iron oxide nanoparticles. EPCs were magnetically labeled with citrate-coated iron oxide nanoparticles. Cell proliferation, migration, and CXCR4 chemokine receptor expression were assessed in different labeling conditions and no adverse effects of the magnetic label were observed. The magnetophoretic mobility of labeled EPCs was determined in vitro, with the same magnet as that subsequently used in vivo. Coronary artery occlusion was induced for 30 min in 36 rats (31 survivors), followed by 20 min of reperfusion. The rats were randomized to receive, during brief aortic cross-clamping, direct intraventricular injection of culture medium (n = 7) or magnetically labeled EPCs (n = 24), with (n = 14) or without (n = 10) subcutaneous insertion of a magnet over the chest cavity (n = 14). The hearts were explanted 24 h later and engrafted cells were visualized by magnetic resonance imaging (MRI) of the heart at 1.5 T. Their abundance in the myocardium was also analyzed semiquantitatively by immunofluorescence, and quantitatively by real-time polymerase chain reaction (RT-PCR).Although differences in cell retention between groups failed to be statistically significant using RT-PCR quantification, due to the variability of the animal model, immunostaining showed that the average number of engrafted EPCs was significantly ten times higher with than without magnetic targeting. There was thus a consistent trend favoring the magnet-treated hearts, thereby suggesting magnetic targeting as a potentially new mean of enhancing myocardial homing of intravascularly delivered stem cells. Magnetic targeting has the potential to enhance myocardial retention of intravascularly delivered endothelial progenitor cells.

Cell surface engineering with polyelectrolyte-stabilized magnetic nanoparticles: A facile approach for fabrication of artificial multicellular tissue-mimicking clusters

“…To date, most published techniques have employed passive internalization of MNPs via endocytosis, which allows for effective magnetic modification of cells [11][12][13]. However, uptake of MNPs by cells entails several major drawbacks, such as (1) a lengthy internalization process, requiring up to 72 h of co-incubation of MNPs with cells [14,15] and (2) potential toxic effects of early-stage cytoplasminternalized nanoparticles [16]. Early reports demonstrate the use of magnetic cationic liposomes (MCLs) fabricated using mixtures of 10-nm magnetite nanoparticles and lipids [5].…”

Visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury

“…After cell transplantation, the non-invasive tracking of cells plays an important role in monitoring the time course of cell migration and the degree of cell homing (Chaudeurge et al, 2012). Cell tracking can provide feedback about the lesion sites and aid in the determination of the optimum number of cells to achieve the desired therapeutic effect (Lijkwan et al, 2010).…”

The Role of Nanotechnology in Induced Pluripotent and Embryonic Stem Cells Research

“…It also enables the guidance and homing of stem cells to target organs using an external magnet placed over the targeted organ. 120 Iron oxide has been transplanted in embryonic stem cells (ESCs) or ESC-derived cardiac precursor cells (ES-CPCs) to label a mouse model of myocardial infarction. [123][124][125][126][127] Feridex and protamine sulfate labeled ESCPCs were also injected into the border zone of heart infarct in mice.…”