Simple SPION Incubation as an Efficient Intracellular Labeling Method for Tracking Neural Progenitor Cells Using MRI

Abstract

Cellular magnetic resonance imaging (MRI) has been well-established for tracking neural progenitor cells (NPC). Superparamagnetic iron oxide nanoparticles (SPIONs) approved for clinical application are the most common agents used for labeling. Conventionally, transfection agents (TAs) were added with SPIONs to facilitate cell labeling because SPIONs in the native unmodified form were deemed inefficient for intracellular labeling. However, compelling evidence also shows that simple SPION incubation is not invariably ineffective. The labeling efficiency can be improved by prolonged incubation and elevated iron doses. The goal of the present study was to establish simple SPION incubation as an efficient intracellular labeling method. To this end, NPCs derived from the neonatal subventricular zone were incubated with SPIONs (Feridex®) and then evaluated in vitro with regard to the labeling efficiency and biological functions. The results showed that, following 48 hours of incubation at 75 µg/ml, nearly all NPCs exhibited visible SPION intake. Evidence from light microscopy, electron microscopy, chemical analysis, and magnetic resonance imaging confirmed the effectiveness of the labeling. Additionally, biological assays showed that the labeled NPCs exhibited unaffected viability, oxidative stress, apoptosis and differentiation. In the demonstrated in vivo cellular MRI experiment, the hypointensities representing the SPION labeled NPCs remained observable throughout the entire tracking period. The findings indicate that simple SPION incubation without the addition of TAs is an efficient intracellular magnetic labeling method. This simple approach may be considered as an alternative approach to the mainstream labeling method that involves the use of TAs.

Synthesis, Characterization, and Toxicity Evaluation of Dextran-Coated Iron Oxide Nanoparticles

“…Surface modifications play an important role in the direct interaction with cells and proteins present in the body fluids and culture medium [49,50]. Furthermore, depending on size, dosage, and exposure time, the nanoparticles can penetrate the biological membranes and reach the target site [51,52].…”

Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations

“…15,[71][72][73] The data and images shown in Figure 1 illustrate the high proportion of bone marrowderived mesenchymal stem cells labeled with SPIONs. In addition to the stem cell tracking, SPIONs have also been used to magnetically target stem cells to lesion sites, as described by Nishida et al 77 Hamasaki et al, 78 successfully showed, in organotypic cultures, the possibility of enhancing axon formation by magnetically localizing SPION-labeled cells.…”

Harnessing magnetic-mechano actuation in regenerative medicine and tissue engineering

“…Long-term success of certain surgical procedures still requires adjuvant therapy to enhance cell retention at a specific site. This can be achieved by labelling stem cells with superparamagnetic iron oxide nanoparticles (SPIONs) and applying a magnetic field to further guide their migration to sites requiring increased cell retention [70,71] (Figure 1D). Importantly, cell labelling with SPIONs appears not to affect viability, proliferation, or specification of MSCs into adipogenic, chondrogenic, or osteogenic lineages under in vivo conditions [72].…”