External magnetic field promotes homing of magnetized stem cells following subcutaneous injection

Abstract

BackgroundMesenchymal stem cells (MSCs) are multipotent stromal cells that have the ability to self-renew and migrate to sites of pathology. In vivo tracking of MSCs provides insights into both, the underlying mechanisms of MSC transformation and their potential as gene delivery vehicles. The aim of our study was to assess the ability of superparamagnetic iron oxide nanoparticles (SPIONs)-labeled Wharton’s Jelly of the human umbilical cord-derived MSCs (WJ-MSCs) to carry the green fluorescent protein (GFP) gene to cutaneous injury sites in a murine model.MethodsWJ-MSCs were isolated from a fresh umbilical cord and were genetically transformed to carry the GFP gene using lentiviral vectors with magnetically labeled SPIONs. The SPIONs/GFP-positive WJ-MSCs expressed multipotent cell markers and demonstrated the potential for osteogenic and adipogenic differentiation. Fifteen skin-injured mice were divided into three groups. Group I was treated with WJ-MSCs, group II with SPIONs/GFP-positive WJ-MSCs, and group III with SPIONs/GFP-positive WJ-MSCs exposed to an external magnetic field (EMF). Magnetic resonance imaging and optical molecular imaging were performed, and images were acquired 1, 2, and 7 days after cell injection.ResultsThe results showed that GFP could be intensively detected around the wound in vivo 24 h after the cells were injected. Furthermore, we observed an accumulation of WJ-MSCs at the wound site, and EMF exposure increased the speed of cell transport. In conclusion, our study demonstrated that SPIONs/GFP function as cellular probes for monitoring in vivo migration and homing of WJ-MSCs. Moreover, exposure to an EMF can increase the transportation efficiency of SPIONs-labeled WJ-MSCs in vivo.ConclusionsOur findings could lead to the development of a gene carrier system for the treatment of diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12860-017-0140-1) contains supplementary material, which is available to authorized users.

Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites

“…Numerous studies have described flow cytometric evaluation of MSC surface markers in order to assess the differentiation potential of MSCs following nanoparticle internalization. 35,[45][46][47][48][49] In agreement with our findings, their results consistently reported no effects on surface-marker expression or osteogenic and adipogenic differentiation ability. These results showed that nanoparticlelabeling did not alter MSC differentiation or characteristics higher than 50 µg/mL did not enhance cell-uptake efficiency, at 100 µg/mL, the nanoparticles tended to aggregate in the culture medium and adhere to the plate.…”

“…Additionally, these represent the first findings of nanoparticles not only promoting CXCR4 expression, 24 but also increasing levels of the migration-related proteins c-Met and CCR1 in MSCs. Although some studies showed that noninvasive EMFs can increase nanoparticleinternalized MSC homing following an intra-arterial or intravenous injection, [34][35][36] there have been no reports showing a similar effect in the absence of EMFs in vivo. However, static magnetic fields can affect MSC viability, 34 proliferation, 37 differentiation capacity, 38 colony formation, 39 and extracellular vesicle secretion.…”

T cells loaded with magnetic nanoparticles are retained in peripheral lymph nodes by the application of a magnetic field

“…Cytometric analyses of MNP-treated T cells showed that APS-MNPs caused no differences in the expression levels of important cell surface markers such as CD62L, CD44, CD11a or CCR7 in Jurkat and primary T cell. These data are in consonance with previous reports showing that MNPs have no significant effect on the expression levels of surface markers of a variety of cells [62–66]. MNPs can trigger cellular activation in some cases [39, 67, 68] but this is mostly due to the nanoparticle design [69].…”

Improving Tumor Retention of Effector Cells in Adoptive Cell Transfer Therapies by Magnetic Targeting

“…A sine qua non condition for MNP-based targeting strategies in ACT to be effective is that the effector lymphoid cells retain their function when loaded with MNPs. Several studies consistently indicate that the expression of surface markers is not significantly affected by MNP presence in a wide variety of cells including lymphoid cells [71,72,78,80,96,[127][128][129]. It thus appears that minimally functionalized MNP (i.e., with a simple chemical coating that allows stable colloidal suspension) do not significantly alter the activity of lymphoid cells.…”