Gene expression profiling reveals early cellular responses to intracellular magnetic labeling with superparamagnetic iron oxide nanoparticles

• Published in: Magnetic resonance in medicine Vol. 63; no. 4; pp. 1031 - 1043
• Main Authors: Kedziorek, Dorota A., Muja, Naser, Walczak, Piotr, Ruiz-Cabello, Jesus, Gilad, Assaf A., Jie, Chunfa C., Bulte, Jeff W. M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2010
• Subjects: Algorithms; Animals; Apoptosis; cell therapy; cell tracking; Contrast Media - chemistry; Detoxification; Dextrans; Ferrosoferric Oxide - chemistry; Gene expression; Gene Expression Profiling; genomics; Heme oxygenase (decyclizing); Homeostasis; Iron; iron metabolism; iron oxides; Lysine - chemistry; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Magnetite Nanoparticles; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Mice; microarray; MR contrast agent; N.M.R; nanoparticles; Neural stem cells; Poly-L-lysine; Polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA - analysis; Stem cells; superparamagnetic iron oxide; Transferrin receptors; zinc-binding protein
• ISSN: 0740-3194; 1522-2594; 1522-2594
• DOI: 10.1002/mrm.22290

With MRI (stem) cell tracking having entered the clinic, studies on the cellular genomic response toward labeling are warranted. Gene expression profiling was applied to C17.2 neural stem cells following superparamagnetic iron oxide/PLL (poly‐L‐lysine) labeling over the course of 1 week. Relative to unlabeled cells, less than 1% of genes (49 total) exhibited greater than 2‐fold difference in expression in response to superparamagnetic iron oxide/PLL labeling. In particular, transferrin receptor 1 (Tfrc) and heme oxygenase 1 (Hmox1) expression was downregulated early, whereas genes involved in lysosomal function (Sulf1) and detoxification (Clu, Cp, Gstm2, Mgst1) were upregulated at later time points. Relative to cells treated with PLL only, cells labeled with superparamagnetic iron oxide/PLL complexes exhibited differential expression of 1399 genes. Though these differentially expressed genes exhibited altered expression over time, the overall extent was limited. Gene ontology analysis of differentially expressed genes showed that genes encoding zinc‐binding proteins are enriched after superparamagnetic iron oxide/PLL labeling relative to PLL only treatment, whereas members of the apoptosis/programmed cell death pathway did not display increased expression. Overexpression of the differentially expressed genes Rnf138 and Abcc4 were confirmed by quantitative real‐time polymerase chain reaction. These results demonstrate that, although early reactions responsible for iron homeostasis are induced, overall neural stem cell gene expression remains largely unaltered following superparamagnetic iron oxide/PLL labeling. Magn Reson Med 63:1031–1043, 2010. © 2010 Wiley‐Liss, Inc.