Amine‐surface‐modified superparamagnetic iron oxide nanoparticles interfere with differentiation of human mesenchymal stem cells

Abstract

Superparamagnetic iron oxide (SPIO) nanoparticles have been widely used for stem cell labeling and tracking. Surface modification has been known to improve biocompatibility, biodistribution, and labeling efficiency of SPIO nanoparticles. However, the effects of amine (NH 3 þ )-surface-modified SPIO nanoparticles on proliferation and differentiation of human mesenchymal stem cells (hMSCs) remain unclear. The purpose of this study is to investigate how amine-surface-modified SPIO nanoparticles affected hMSCs. In this study, intracellular uptake and the contiguous presence of amine-surface-modified SPIO nanoparticles in hMSCs were demonstrated by Prussian blue staining, transmission electron microscopy and magnetic resonance imaging. Moreover, accelerated cell proliferation was found to be associated with cellular internalization of amine-surface-modified SPIO nanoparticles. The osteogenic and chondrogenic differentiation potentials of hMSCs were impaired after treating with SPIO, while adipogenic potential was relatively unaffected. Altered cytokine production profile in hMSCs caused by amine-surface-modified SPIO nanoparticles may account for the increased proliferation and impaired differentiation potentials; concentrations of the growth factors in the SPIO-labeled condition medium including amphiregulin, glial cell-derived neurotrophic factor, heparin-binding EGF-like growth factor and vascular endothelial growth factor, as well as soluble form of macrophage colony-stimulating factor receptor and SCF receptor, were higher than in the unlabeled-condition medium. In summary, although amine-surface-modified SPIO labeling is effective for cell tracking, properties of hMSCs may alter as a consequence and this needs to be taken into account when evaluating therapeutic efficacies of SPIO-labeled stem cells in vivo. ß

Comparative In Vitro Study on Magnetic Iron Oxide Nanoparticles for MRI Tracking of Adipose Tissue-Derived Progenitor Cells

“…Apparently, BNF starch at high labeling concentrations disabled cells completely to generate three-dimensional pellets. These results are in line with several other studies analyzing the effect of iron oxide nanoparticles on chondrogenesis [14], [30], [55]. Whereas it was reported that SPIO labeling interfered with the organization of F-actin resulting in a dose-dependent impairment of chondrogenesis [30], F-actin staining of nanoparticle-labeled cells did not reveal any disorganization of F-actin (data not shown).…”

Mesenchymal stromal cell labeling by new uncoated superparamagnetic maghemite nanoparticles in comparison with commercial Resovist – an initial in vitro study

“…Several traditional contrast agents have been withdrawn from the market 7 recently or have displayed insufficient biocompatibility. 24,25 Thus, the quest to fabricate economically accessible and yet efficient new contrast probes has taken on great importance. Our bare stoichiometric maghemite (γ-Fe 2 O 3 ) nanoparticles are named "SAMNs" because their most prominent characteristic is their ability to form stable colloidal suspensions in water without any organic or inorganic coating.…”

Biological characteristics of adipose tissue‐derived stem cells labeled with amine‐surface‐modified superparamagnetic iron oxide nanoparticles

“…Positively charged transfection agents such as polylysine and protamine sulfate have been used to increase cellular iron uptake. Unfortunately, most transfection reagents have limited clinical application due to their cytotoxicity Chang et al, 2012). Moreover, to our knowledge, there have been no studies on investigating the side effects of SPIO nanoparticles on liver, kidney, and spleen tissue after cell transplantation.…”