Magnetic Targeting of Human Mesenchymal Stem Cells with Internalized Superparamagnetic Iron Oxide Nanoparticles

Abstract

Cell therapies offer exciting new opportunities for effectively treating many human diseases. However, delivery of therapeutic cells by intravenous injection, while convenient, relies on the relatively inefficient process of homing of cells to sites of injury. To address this limitation, a novel strategy has been developed to load cells with superparamagnetic iron oxide nanoparticles (SPIOs), and to attract them to specific sites within the body by applying an external magnetic field. The feasibility of this approach is demonstrated using human mesenchymal stem cells (hMSCs), which may have a significant potential for regenerative cell therapies due to their ease of isolation from autologous tissues, and their ability to differentiate into various lineages and modulate their paracrine activity in response to the microenvironment. The efficient loading of hMSCs with polyethylene glycol-coated SPIOs is achieved, and it is found that SPIOs are localized primarily in secondary lysosomes of hMSCs and are not toxic to the cells. Further, the key stem cell characteristics, including the immunophenotype of hMSCs and their ability to differentiate, are not altered by SPIO loading. Through both experimentation and mathematical modeling, it is shown that, under applied magnetic field gradients, SPIO-containing cells can be localized both in vitro and in vivo. The results suggest that, by loading SPIOs into hMSCs and applying appropriate magnetic field gradients, it is possible to target hMSCs to particular vascular networks.

Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?

“…After chemo-and radio-therapy, there are increased levels of SDF-1 in the bone marrow, thus increasing its attraction for HSCs and MSCs [126] . There are also reports of manipulating MSC migration with ultrasound or magnetic or electric fields [127][128][129] . However, these techniques do not appear to be very practical and they need adequate expression of homing molecules.…”

“…On the other hand, ultrasound-guided delivery might be more challenging in deep organs. Finally, homing directed by a magnetic field might require the implantation of a magnet in or near the tissue of interest [127][128][129] .…”

Innovative superparamagnetic iron-oxide nanoparticles coated with silica and conjugated with linoleic acid: Effect on tumor cell growth and viability

“…SPIONs can be internalized in human mesenchymal stem cells without affecting viability and structure. Following this, the SPION-loaded stem cells can be attracted to specific sites by applying an external magnetic field [8].…”

Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles

“…A variety of cell types have demonstrated the ability to safely endocytose SPIONs including mesenchymal stem cells 35 , endothelial progenitor cells 36 , beta islet cells 37 , and neural stem cells 38 . Magnetic cell targeting may be preferred over other cell targeting techniques when a high degree of control over the delivery conditions is necessary.…”