Abstract
Cell-based therapy with mesenchymal stem cells (MSCs) is a promising strategy for acute ischemic stroke. In vivo tracking of therapeutic stem cells with magnetic resonance imaging (MRI) is imperative for better understanding cellular survival and migrational dynamics over time. In this study, we develop a novel biocompatible nanocomplex (ASP-SPIONs) based on cationic amylose, by introducing spermine and the image label, ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs), to label MSCs. The capacity, efficiency, and cytotoxicity of the nanocomplex in transferring SPIONs into green fluorescence protein-modified MSCs were tested; and the performance of in vivo MRI tracking of the transplanted cells in acute ischemic stroke was determined. The results demonstrated that the new class of SPIONs-complexed nanoparticles based on biodegradable amylose can serve as a highly effective and safe carrier to transfer magnetic label into stem cells. A reliable tracking of transplanted stem cells in stroke was achieved by MRI up to 6 weeks, with the desirable therapeutic benefit of stem cells on stroke retained. With the advantages of a relatively low SPIONs concentration and a short labeling period, the biocompatible complex of cationic amylose with SPIONs is highly translatable for clinical application. It holds great promise in efficient, rapid, and safe labeling of stem cells for subsequent cellular MRI tracking in regenerative medicine.
Highlights
Stem cell transplantation has emerged as a promising therapeutic strategy for numerous human diseases, including ischemic stroke, owing to their inherent capacity of self-renewing, homing, and multi-lineage differentiating [1,2]
Previous studies have proven the potential of mesenchymal stem cells (MSCs) to regenerate neural cells after being grafted into the central nervous system (CNS), MSCs have been investigated as an alternative candidate for treatment of CNS disorders, including stroke [5]
Our results suggested that cationic ASP-superparamagnetic iron oxide nanoparticles (SPIONs) offers a rapid and highly efficient approach for the magnetic labeling of MSCs, enabling in vivo Magnetic resonance imaging (MRI) tracking of transplanted cells in stroke
Summary
Stem cell transplantation has emerged as a promising therapeutic strategy for numerous human diseases, including ischemic stroke, owing to their inherent capacity of self-renewing, homing, and multi-lineage differentiating [1,2]. Cellular therapy with the use of MSCs could obviate the need for acquiring autologous human neural stem cells for the nervous system, which is an admittedly difficult procedure. Imaging of transplanted stem cells in a non-invasive manner is essential because it can provide insight into cellular proliferation dynamics, biodistribution, migrational dynamics, differentiation processes, and participation in tissue repair [7]. For cellular MRI, direct cell labeling with superparamagnetic iron oxide nanoparticles (SPIONs) became the most commonly used strategy in terms of the biocompatibility, low toxicity, and high sensitivity of SPIONs. the unmodified SPIONs could not be efficiently up-taken by non-phagocytic stem cells per se [9,10]. Cell labeling with TAs has saturation effects, requiring a high concentration of TAs and a long incubation period, which would pose a negative effect to cell biological behaviors after their transplantation [13]
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