Ning Pei

Deep magnetic capture of magnetically loaded cells for spatially targeted therapeutics

Magnetic targeting has recently demonstrated potential in promoting magnetically loaded cell delivery to target lesion, but its application is limited by magnetic attenuation. For deep magnetic capture of cells for spatial targeting therapeutics, we designed a magnetic pole, in which the magnetic field density can be focused at a distance from the pole. As flowing through a tube served as a model of blood vessels, the magnetically loaded mesenchymal stem cells (MagMSCs) were highly enriched at the site distance from the magnetic pole. The cell capture efficiency was positively influenced by the magnetic flux density, and inversely influenced by the flow velocity, and well-fitted with the deductive value by theoretical considerations. It appeared to us that the spatially-focused property of the magnetic apparatus promises a new deep targeting strategy to promote homing and engraftment for cellular therapy.

Magnetic targeting enhances retrograde cell retention in a rat model of myocardial infarction

IntroductionRetrograde coronary venous infusion is a promising delivery method for cellular cardiomyoplasty. Poor cell retention is the major obstacle to the establishment of this method as the preferred route for cell delivery. Here, we explored whether magnetic targeting could enhance retrograde cell retention in a rat model of myocardial infarction.MethodsRat mesenchymal stem cells were labeled with superparamagnetic oxide nanoparticles. The magnetic responsiveness of MSCs was observed while cells flowed through a tube that served as a model of blood vessels in a 0.6-Tesla magnetic field. In a Sprague–Dawley rat model of acute myocardial infarction, 1 × 106 magnetic mesenchymal stem cells were transjugularly injected into the left cardiac vein while a 0.6-Tesla magnet was placed above the heart. The cardiac retention of transplanted cells was assessed by using quantitative Y chromosome-specific polymerase chain reaction, cardiac magnetic resonance imaging, and optical imaging. Cardiac function was measured by using echocardiography, and histologic analyses of infarct morphology and angiogenesis were obtained.ResultsThe flowing iron oxide-labeled mesenchymal stem cells were effectively attracted to the area where the magnet was positioned. Twenty-four hours after cellular retrocoronary delivery, magnetic targeting significantly increased the cardiac retention of transplanted cells by 2.73- to 2.87-fold. Histologic analyses showed that more transplanted cells were distributed in the anterior wall of the left ventricle. The enhanced cell engraftment persisted for at least 3 weeks, at which time, left ventricular remodeling was attenuated, and cardiac function benefit was improved.ConclusionsThese results suggest that magnetic targeting offers new perspectives for retrograde coronary venous delivery to enhance cell retention and subsequent functional benefit in heart diseases.

The effect of nonuniform magnetic targeting of intracoronary-delivering mesenchymal stem cells on coronary embolisation.

Magnetic targeting has been recently introduced to enhance cell retention in animals with acute myocardial infarction. However, it is unclear whether the magnetic accumulation of intravascular cells increases the risk of coronary embolism. Upon finite element analysis, we found that the permanent magnetic field was nonuniform, manifestated as attenuation along the vertical axis and polarisation along the horizontal axis. In the in vitro experiments, iron-labelled mesenchymal stem cells (MSCs) were accumulated in layers predominantly at the edge of the magnet. In an ischaemic rat model subjected to intracavitary MSCs injection, magnetic targeting induced unfavourable vascular embolisation and an inhomogeneous distribution of the donor cells, which prevented the enhanced cell retention from translating into additional functional benefit. These potential complications of magnetic targeting should be thoroughly investigated and overcome before clinical application.

Comparison of Magnetic Intensities for Mesenchymal Stem Cell Targeting Therapy on Ischemic Myocardial Repair: High Magnetic Intensity Improves Cell Retention but Has no Additional Functional Benefit.

Magnetic targeting has the potential to enhance the therapeutic effects of stem cells through increasing retention of transplanted cells. To investigate the effects of magnetic targeting intensities on cell transplantation, we performed different magnetic intensities for mesenchymal stem cell (MSC)-targeting therapy in a rat model of ischemia/reperfusion. Rat MSCs labeled with superparamagnetic oxide nanoparticles (SPIOs) were injected into the left ventricular (LV) cavity of rats during a brief aorta and pulmonary artery occlusion. The 0.15 Tesla (T), 0.3 T, and 0.6 T magnets were placed 0~1 mm above the injured myocardium during and after the injection of 1 × 106 MSCs. Fluorescence imaging and quantitative PCR revealed that magnetic targeting enhanced cell retention in the heart at 24 h in a magnetic field strength-dependent manner. Compared with the 0 T group, three magnetic targeting groups enhanced varying cell engraftment at 3 weeks, at which time LV remodeling was maximally attenuated, and the therapeutic benefit (LV ejection fraction) was also highest in the 0.3 T groups. Interestingly, due to the low MSC engraftment resulting from microvascular embolisms, the 0.6 T group failed to translate into additional therapeutic outcomes, though it had the highest cell retention. Magnetic targeting enhances cell retention in a magnetic field strength-dependent manner. However, too high of a magnetic intensity may result in microembolization and consequently undermine the functional benefits of cell transplantation.

A novel method to delivery stem cells to the injured heart: spatially focused magnetic targeting strategy.

Given the adult hearts minimal capacity for endogenous regeneration, cell therapy has emerged as a promising approach to the regeneration of damaged vascular and cardiac tissue after acute myocardial infarction and heart failure. However, systematic review suggests only mild improvement in global heart function, and high degree of heterogeneity among clinical trials [1]. The first prerequisite for cell therapy success is the engraftment and thus, homing of transplanted cells to the target area. Poor cell homing, retention and engraftment are major obstacles in achieving a significant functional benefit irrespective of the cell type or delivery route used. Data showed only 1–3% of the delivered cells were recruited at the infarct sites via intracoronary administration. The retention of cells in the heart is extremely low, even undetectable after a few weeks when administered by the intravenous route [2,3,4,5]. The predominant number of cells was found in non-targeting organs such as liver, spleen and lung. To induce migration and homing of transplanted cells to optimize the efficacy of cell-based therapies, much efforts have been made in identifying chemokine and its receptors (CXCR4/SDF-1 axis, et al.) in the last decades [6,7]. However, due to the extreme complicity of the ‘cell-extracellular matrix-cytokine’ network and the homing molecular mechanisms, the chemoattractant molecules-targeted method has been far away from being able to precisely and effectively regulate stem cell migrating to target tissue [8,9]. Magnetic targeting strategy, traditionally used in chemotherapy for tumour [10], had been introduced to localize magnetic nanoparticle-loaded cell delivery to target lesion in vivo in recent years [11,12,13,14,15,16,17]. The accumulation and retention of the magnetic responsive cells can be enhanced by using an external magnetic field produced by electromagnet, which is focused on the area of interest [18]. Cheng K. et al. [19 were the first to introduce magnetic targeting strategy to attract transplanted cells to the heart. Using a 1.3 Tesla magnet applied above the rat apex during the intramyocardial injection of magnetic responsive cardiosphere-derived cells, they found that cell retention and engraftment in the recipient hearts increased by approximately threefold compared to non-targeted cells. Chaudeurge A et al. 2011 adopted subcutaneous insertion of a magnet over the chest cavity during therapeutic intracavitary stem cell infusion, found that the average number of engrafted cells was significantly 10 times higher with than without magnetic targeting. This magnetically enhanced intracoronary cell delivery was confirmed by another study 2012. Thus, magnetic targeting is proved to enhance cell retention, engraftment and this novel method to improve cell therapy outcome offers the potential for clinical applications. However, the magnetic field has some inherent limitations as the magnetic flux density is maximal at the magnet pole face and cannot be focused at a distance from the magnet [10]. For conventional electromagnet therefore magnetically loaded cells are predominantly attracted to the surface of magnetic materials, and hard to be targeted to tissues localized deeper in the body. To promote the cell retention at targeting sites remote from the magnet surface, a greater magnetic force or invasive approaches (e.g. implant magnetized stent, magnetic particles or magnet at the target site) will be required. Magnetically loaded endothelial cells were homing to the magnetized stent deployed in rat arteries in the presence of a uniform magnetic field [12,13]. However, achievement of the cell engraftment necessary for therapeutic effects by using a ‘safe magnet force’ would be challenging. Moreover, it is not feasible that there could be the invasive implantation of a magnet or magnetized materials in parenchymatous organs such as heart. To overcome these limitations, it is of great significance to develope a magnetic field which can be focused at a distance from the magnet surface. Recently, we proposed that the spatially focused magnetic field is feasible in theoretical considerations [22]. Its deep capture property of this special magnetic field has been testified in our preliminary in vitro study [22,23]. The deep accumulation of magnetically loaded mesenchymal stem cells was observed while cells flowed through a tube served as a model of blood vessels in such a magnetic field. The cell capture efficiency was positively influenced by the magnetic flux density, and negatively influenced by the flow velocity. The capture efficiency reached 89.3% with 640 mT of the magnetic flux density, 38.4 T/m of the magnetic intensity gradient and 0.8 mm/sec. of flow velocity in our in vitro study [23].

Aggregation process of paramagnetic particles in fluid in the magnetic field

Magnetic targeting is a promising therapeutic strategy for localizing systemically delivered magnetic responsive drugs or cells to target tissue, but excessive aggregation of magnetic particles could result in vascular embolization. To analyze the reason for embolization, the attractive process of magnetic particles in magnetic field (MF) was studied in this paper by analyzing the form of the aggregated paramagnetic particles while the particle suspension flowed through a tube, which served as a model of blood vessels. The effects of magnetic flux density and fluid velocity on the formation of aggregated paramagnetic particles were investigated. The number of large aggregated clusters dramatically increased with increment in the magnetic flux density and decreased with increment in the fluid velocity. The analysis of accumulative process demonstrates the MF around initially attracted particles was focused, which induced the formation of clusters and increased the possibility of embolism. Bioelectromagnetics. 37:323-330, 2016.

Electric current pulse induced grain refinement in pure aluminium

Abstract In the present work, pure aluminium melt was treated using electric current pulse. The effect of current density on the solidification microstructure was investigated by means of wire netting technology. It was found that wire netting could not only effectively stop crystal nucleus to enter other zones but also has relatively small effects on the heat transfer and convection in melts. Theoretical analysis and ANSYS simulation suggested that variation of current density in different localised zones is a key factor influencing the microstructural features. Increasing the current density is favourable for the formation of equiaxed grains.

Deep Capture of Paramagnetic Particle for Targeting Therapeutics

Magnetic targeting, a promising therapeutic strategy for localizing systemically-delivered drug to target tissue, is limited by magnetic attenuation. A special apparatus was developed to fulfill deep magnetic targeting. Due to special shape of poles and magnetic shields, the magnetic field produced by this apparatus was stronger at the center of the air gap than any other place along two directions. The magnetic field could make deep capturing along these directions. To test the aggregation property of this apparatus, the accumulation of 500-nm paramagnetic particles was observed as flowing through a tube served as a model of blood vessels. The relationship of the accumulation of the paramagnetic particles and effectiveness of the magnetic shielding was studied. KeywordsMagnetic drug targeting; Paramagnetic particles; In vitro

Effect of flow on solidification structure of pure aluminium under pulse magneto-oscillation

ABSTRACT This paper reports on the processing of aluminium melt by pulse magneto-oscillation (PMO) technology. The melt is divided into five layers using a layered isolation device and, after grinding and corrosion, the refining effects of equiaxed crystals are observed to decrease from the centre outwards. The electromagnetic force and flow velocity of the melt were simulated using the ANSYS package, and found to decrease in the same manner as crystal size; i.e. from the centre outwards. It was also found that the melt, treated by PMO, possessed an optimum characteristic length at which the flow velocity reaches a maximum value, thus improving the refining effect of the solidification structure of the melt.

Uniform magnetic targeting of magnetic particles attracted by a new ferromagnetic biological patch: Targeting Particles by Ferromagnetic Patch

A new non-toxic ferromagnetic biological patch (MBP) was designed in this paper. The MBP consisted of two external layers that were made of transparent silicone, and an internal layer that was made of a mixture of pure iron powder and silicon rubber. Finite-element analysis showed that the local inhomogeneous magnetic field (MF) around the MBP was generated when MBP was placed in a uniform MF. The local MF near the MBP varied with the uniform MF and shape of the MBP. Therefore, not only could the accumulation of paramagnetic particles be adjusted by controlling the strength of the uniform MF, but also the distribution of the paramagnetic particles could be improved with the different shape of the MBP. The relationship of the accumulation of paramagnetic particles or cells, magnetic flux density, and fluid velocity were studied through in vitro experiments and theoretical considerations. The accumulation of paramagnetic particles first increased with increment in the magnetic flux density of the uniform MF. But when the magnetic flux density of the uniform MF exceeded a specific value, the magnetic flux density of the MBP reached saturation, causing the accumulation of paramagnetic particles to fall. In addition, the adsorption morphology of magnetic particles or cells could be improved and the uniform distribution of magnetic particles could be achieved by changing the shape of the MBP. Also, MBP may be used as a new implant to attract magnetic drug carrier particles in magnetic drug targeting. Bioelectromagnetics. 39:98-107, 2018.