Biocompatible Iron Oxide Nanoring-Labeled Mesenchymal Stem Cells: An Innovative Magnetothermal Approach for Cell Tracking and Targeted Stroke Therapy

Abstract

Labeling stem cells with magnetic nanoparticles is a promising technique for <i>in vivo</i> tracking and magnetic targeting of transplanted stem cells, which is critical for improving the therapeutic efficacy of cell therapy. However, conventional endocytic labeling with relatively poor labeling efficiency and a short labeling lifetime has hindered the implementation of these innovative enhancements in stem-cell-mediated regenerative medicine. Herein, we describe an advanced magnetothermal approach to label mesenchymal stem cells (MSCs) efficiently by local induction of heat-enhanced membrane permeability for magnetic resonance imaging (MRI) tracking and targeted therapy of stroke, where biocompatible γ-phase, ferrimagnetic vortex-domain iron oxide nanorings (γ-FVIOs) with superior magnetoresponsive properties were used as a tracer. This approach facilitates a safe and efficient labeling of γ-FVIOs as high as 150 pg of Fe per cell without affecting the MSCs proliferation and differentiation, which is 3.44-fold higher than that by endocytosis labeling. Such a high labeling efficiency not only enables the ultrasensitive magnetic resonance imaging (MRI) detection of sub-10 cells and long-term tracking of transplanted MSCs over 10 weeks but also endows transplanted MSCs with a magnetic manipulation ability <i>in vivo</i>. A proof-of-concept study using a rat stroke model showed that the labeled MSCs facilitated MRI tracking and magnetic targeting for efficient replacement therapy with a significantly reduced dosage of 5 × 10⁴ transplanted cells. The findings in this study have demonstrated the great potential of the magnetothermal approach as an efficient labeling technique for future clinical usage.