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1.  Influence of Iron Oxide Nanoparticles on Innate and Genetically Modified Secretion Profiles of Mesenchymal Stem Cells 
IEEE transactions on magnetics  2013;49(1):389-393.
Mesenchymal stem cells (MSCs) have well-established paracrine effects that are proving to be therapeutically useful. This potential is based on the ability of MSCs to secrete a range of neuroprotective and anti-inflammatory molecules. Previous work in our laboratory has demonstrated that intravenous injection of MSCs, treated with superparamagnetic iron oxide nanoparticle fluidMAG-D resulted in enhanced levels of glial-derived neurotrophic factor, ciliary neurotrophic factor, hepatocyte growth factor and interleukin-10 in the dystrophic rat retina. In this present study we investigated whether the concentration of fluidMAG-D in cell culture media affects the secretion of these four molecules in vitro. In addition, we assessed the effect of fluidMAG-D concentration on retinoschisin secretion from genetically modified MSCs. ELISA-assayed secretion of these molecules was measured using escalating concentrations of fluidMAG-D which resulted in MSC iron loads of 0, 7, 120, or 274 pg iron oxide per cell respectively. Our results demonstrated glial-derived neurotrophic factor and hepatocyte growth factor secretion was significantly decreased but only at the 96 hour’s time-point whereas no statistically significant effect was seen with ciliary neurotrophic factor secretion. Whereas no effect was observed on culture media concentrations of retinoschisin with increasing iron oxide load, a statistically significant increase in cell lysate retinoschisin concentration (p = 0.01) was observed suggesting that increasing fluidMAG-D concentration did increase retinoschisin production but this did not lead to greater secretion. We hypothesize that higher concentrations of iron-oxide nanoparticle fluidMAG-D have an effect on the innate ability of MSCs to secrete therapeutically useful molecules and also on secretion from genetically modified cells. Further work is required to verify these in vitro finding using in vivo model systems.
doi:10.1109/TMAG.2012.2225829
PMCID: PMC4072646  PMID: 24976643 CAMSID: cams4161
Blindness; magnetic nanoparticles; retina; stem cells
2.  Crucial Ignored Parameters on Nanotoxicology: The Importance of Toxicity Assay Modifications and “Cell Vision” 
PLoS ONE  2012;7(1):e29997.
Until now, the results of nanotoxicology research have shown that the interactions between nanoparticles (NPs) and cells are remarkably complex. In order to get a deep understanding of the NP-cell interactions, scientists have focused on the physicochemical effects. However, there are still considerable debates about the regulation of nanomaterials and the reported results are usually in contradictions. Here, we are going to introduce the potential key reasons for these conflicts. In this case, modification of conventional in vitro toxicity assays, is one of the crucial ignored matter in nanotoxicological sciences. More specifically, the conventional methods neglect important factors such as the sedimentation of NPs and absorption of proteins and other essential biomolecules onto the surface of NPs. Another ignored matter in nanotoxicological sciences is the effect of cell “vision” (i.e., cell type). In order to show the effects of these ignored subjects, we probed the effect of superparamagnetic iron oxide NPs (SPIONs), with various surface chemistries, on various cell lines. We found thatthe modification of conventional toxicity assays and the consideration of the “cell vision” concept are crucial matters to obtain reliable, and reproducible nanotoxicology data. These new concepts offer a suitable way to obtain a deep understanding on the cell-NP interactions. In addition, by consideration of these ignored factors, the conflict of future toxicological reports would be significantly decreased.
doi:10.1371/journal.pone.0029997
PMCID: PMC3254623  PMID: 22253854
3.  Process and formulation variables in the preparation of injectable and biodegradable magnetic microspheres 
The aim of this study was to prepare biodegradable sustained release magnetite microspheres sized between 1 to 2 μm. The microspheres with or without magnetic materials were prepared by a W/O/W double emulsion solvent evaporation technique using poly(lactide-co-glycolide) (PLGA) as the biodegradable matrix forming polymer. Effects of manufacturing and formulation variables on particle size were investigated with non-magnetic microspheres. Microsphere size could be controlled by modification of homogenization speed, PLGA concentration in the oil phase, oil phase volume, solvent composition, and polyvinyl alcohol (PVA) concentration in the outer water phase. Most influential were the agitation velocity and all parameters that influence the kinematic viscosity of oil and outer water phase, specifically the type and concentration of the oil phase. The magnetic component yielding homogeneous magnetic microspheres consisted of magnetite nanoparticles of 8 nm diameter stabilized with a polyethylene glycole/polyacrylic acid (PEG/PAA) coating and a saturation magnetization of 47.8 emu/g. Non-magnetic and magnetic microspheres had very similar size, morphology, and size distribution, as shown by scanning electron microscopy. The optimized conditions yielded microspheres with 13.7 weight% of magnetite and an average diameter of 1.37 μm. Such biodegradable magnetic microspheres seem appropriate for vascular administration followed by magnetic drug targeting.
doi:10.1186/1477-044X-5-2
PMCID: PMC1863415  PMID: 17407608

Results 1-3 (3)