Highly efficient magnetic targeting of mesenchymal stem cells in spinal cord injury

Abstract

Abstract:The transplantation of mesenchymal stem cells (MSC) is currently under study as a therapeutic approach for spinal cord injury, and the number of transplanted cells that reach the lesioned tissue is one of the critical parameters. In this study, intrathecally transplanted cells labeled with superparamagnetic iron oxide nanoparticles were guided by a magnetic field and successfully targeted near the lesion site in the rat spinal cord. Magnetic resonance imaging and histological analysis revealed significant differences in cell numbers and cell distribution near the lesion site under the magnet in comparison to control groups. The cell distribution correlated well with the calculated distribution of magnetic forces exerted on the transplanted cells in the subarachnoid space and lesion site. The kinetics of the cells' accumulation near the lesion site is described within the framework of a mathematical model that reveals those parameters critical for cell targeting and suggests ways to enhance the efficiency of magnetic cell delivery. In particular, we show that the targeting efficiency can be increased by using magnets that produce spatially modulated stray fields. Such magnetic systems with tunable geometric parameters may provide the additional level of control needed to enhance the efficiency of stem cell delivery in spinal cord injury.

The effects of grafted mesenchymal stem cells labeled with iron oxide or cobalt-zinc-iron nanoparticles on the biological macromolecules of rat brain tissue extracts

“…Adherent cells during subsequent passages were differentiated into adipoblasts, osteoblasts, and chondroblasts. 12,13 Flow cytometry revealed strong positivity for CD90 and weak positivity for CD105, but cells were negative for CD3, CD34, CD45RA, and CD73 (Turnovcova, unpublished data, 2015). In culture, the cells were positive for CD90 and fibronectin and negative for CD11b and CD45.…”

Nanoparticle Technologies in the Spinal Cord

“…Magnetofection at precise locations in the spinal cord can be accomplished in vivo using superparamagnetic iron oxide nanoparticles [Song et al, 2010]. Iron oxide magnetically labeled bone marrow stromal cells [Nishida et al, 2006;Sasaki et al, 2011] and mesenchymal stem cells [Vanecek et al, 2012;Tukmachev et al, 2015] were targeted to spinal cord lesions using magnetic fields. Additionally, high-frequency magnetic fields can be used to heat iron oxide nanoparticles in order to induce hyperthermia, which can destroy tumor cells [Hergt and Dutz, 2007].…”

Mesenchymal Stem Cells as Immune Modulators in VCA

“…As MSCs have been shown to take residence in perivascular space [6,8], they serve as ideal candidates for promotion of the endothelial barrier properties that are necessary to limit cytotoxic damage and influx of immune cells that prime the rejection response. Novel strategies to improve MSC targeting have been discussed in the literature [17,23,35,108,114,122] including hypoxic/pharmacologic preconditioning [122], genetic engineering of MSCs [17], and magnetic-based guidance [23,35,108,114] to focus delivery to the region of interest using systemic delivery after the inciting inflammatory event. Recent work has proposed a new approach that can utilize MSC-based cell therapy to modify the allograft itself at the time of transplantation to facilitate graft tolerance [16,76,78,100,101] (Fig.…”