Evaluation of Intracellular Labeling with Micron-Sized Particles of Iron Oxide (MPIOs) as a General Tool for In Vitro and in Vivo Tracking of Human Stem and Progenitor Cells

Abstract

Magnetic resonance imaging (MRI)-based tracking is increasingly attracting attention as a means of better understanding stem cell dynamics in vivo. Intracellular labeling with micrometer-sized particles of iron oxide (MPIOs) provides a practical MRI-based approach due to superior detectability relative to smaller iron oxide particles. However, insufficient information is available about the general utility across cell types and the effects on cell vitality of MPIO labeling of human stem cells. We labeled six human cell types from different sources: mesenchymal stem cells derived from bone marrow (MSCs), mesenchymal stem cells derived from adipose tissue (ASCs), presumptive adult neural stem cells (ad-NSCs), fetal neural progenitor cells (f-NPCs), a glioma cell line (U87), and glioblastoma tumor stem cells (GSCs), with two different sizes of MPIOs (0.9 and 2.84 µm). Labeling and uptake efficiencies were highly variable among cell types. Several parameters of general cell function were tested in vitro. Only minor differences were found between labeled and unlabeled cells with respect to proliferation rate, mitotic duration, random motility, and capacity for differentiation to specific phenotypes. In vivo behavior was tested in chicken embryos and severe combined immunodeficient (SCID) mice. Postmortem histology showed that labeled cells survived and could integrate into various tissues. MRI-based tracking over several weeks in the SCID mice showed that labeled GSCs and f-NPCs injected into the brain exhibited translocations similar to those seen for unlabeled cells and as expected from migratory behavior described in previous studies. The results support MPIO-based cell tracking as a generally useful tool for studies of human stem cell dynamics in vivo.

Viability, Differentiation Capacity, and Detectability of Super-Paramagnetic Iron Oxide-Labeled Muscle Precursor Cells for Magnetic-Resonance Imaging

“…[23][24][25][27][28][29][30] As not only labeling efficiency, but also cell survival and behavior appears cell and SPIO dependent, proliferation and differentiation analysis should be considered when labeling stem cells with SPIO. [31][32][33][34] In this study, we demonstrate the labeling of hMPCs with SPIO nanoparticles without additional transfection agents and evaluate the possibility to track these cells over time in a noninvasive manner. We present data defining the optimal concentration for SPIO labeling without a negative effect on viability, differentiation, and myofiber formation.…”

Multimodal imaging of micron‐sized iron oxide particles following in vitro and in vivo uptake by stem cells: down to the nanometer scale

“…They require high uptake efficiency to generate sufficient contrast and suffer from background migration, which is nanoparticle migration independent of the migrating cells (2). Therefore micron-sized paramagnetic iron oxide (MPIO) particles have gained increasing interest (9)(10)(11)(12). The most important reason for this is that MPIO generate single particle contrast in MRI (7).…”

“…Some effects, such as the effect of cell labeling on cellular functions and biodegradation, have been studied in much detail, but very often only in vitro (12,(15)(16)(17)(18)(19)(20). Several studies have assessed cell labeling with MPIO specifically and have shown no deleterious effects on cellular functions in vitro (12,(18)(19)(20).…”

“…Moreover their fluorescent label is integrated in the particle. MPIO-labeling has not shown toxicity and MPIO can also easily be functionalized, leading to an improved and/or more targeted uptake (1,(12)(13)(14).…”

“…Several studies have assessed cell labeling with MPIO specifically and have shown no deleterious effects on cellular functions in vitro (12,(18)(19)(20).…”