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

Abstract

Magnetic resonance imaging (MRI) using measurement of the transverse relaxation time (R2*) is to be considered as a promising approach for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. While the relationship between core composition of nanoparticles and their MRI properties is well studied, little is known about possible effects on progenitor cells. This in vitro study aims at comparing two magnetic iron oxide nanoparticle types, single vs. multi-core nanoparticles, regarding their physico-chemical characteristics, effects on cellular behavior of adipose tissue-derived stem cells (ASC) like differentiation and proliferation as well as their detection and quantification by means of MRI. Quantification of both nanoparticle types revealed a linear correlation between labeling concentration and R2* values. However, according to core composition, different levels of labeling concentrations were needed to achieve comparable R2* values. Cell viability was not altered for all labeling concentrations, whereas the proliferation rate increased with increasing labeling concentrations. Likewise, deposition of lipid droplets as well as matrix calcification revealed to be highly dose-dependent particularly regarding multi-core nanoparticle-labeled cells. Synthesis of cartilage matrix proteins and mRNA expression of collagen type II was also highly dependent on nanoparticle labeling. In general, the differentiation potential was decreased with increasing labeling concentrations. This in vitro study provides the proof of principle for further in vivo tracking experiments of progenitor cells using nanoparticles with different core compositions but also provides striking evidence that combined testing of biological and MRI properties is advisable as improved MRI properties of multi-core nanoparticles may result in altered cell functions.

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

“…On the contrary, other groups have demonstrated that SPIO nanoparticles have little toxicity and few side effects on cell activity and proliferation (Suh et al, 2009;Crabbe et al, 2010). A recent study revealed that improved MRI properties of multi-core nanoparticles may result in altered cell functions (Kasten et al, 2014). In addition, an inhibitory effect of SPIO nanoparticles on MSCs differentiation and signaling mechanisms has been reported .…”

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro

“…As a rule, in vitro cytotoxicity tests are conducted using exposure times up to 24 h. Furthermore, the long-term tests are not common with NPs, even though long-term cytotoxicity tests are not rare (Wagner et al 2009;Kasten et al 2014;Müller et al 2007). It has been discussed that there could be a linear correlation between short and long-term toxicity (Scheers et al 2001).…”

Toxicity and Functional Impairment in Human Adipose Tissue-Derived Stromal Cells (hASCs) Following Long-Term Exposure to Very Small Iron Oxide Particles (VSOPs)

“…Information on the influence of IONPs exposition and their intracellular accumulation on the functional capabilities of hASCs is still incomplete and partially controversial [14,43,44]. Our study group previously demonstrated the intracellular accumulation and persistence of ZnO-NPs in hASCs after long-term cultivation [34,45].…”

“…Stroh et al, who used the same concentration of the same IONPs, also found no effect on the cell viability of haNSCs and murine embryonic stem cells (mESC) 8 h and 48 h after the labelling procedure [3]. Some authors describe a concentration-dependent impairment of the viability of ASCs, BMSCs and other cell types after labelling or exposure to IONPs [3,15,47,48], which is thought to be mediated by various cellular changes such as oxidative stress [3,15,42,44,47,49].…”