Evaluation of the homing of human CD34+ cells in mouse bone marrow using clinical MR imaging

There have been several reports using various superparamagnetic iron oxide (SPIO) nanoparticles to label mammalian cells for monitoring their temporal and spatial migration in vivo by Magnetic Resonance Imaging (MRI). The purpose of this study was to evaluate the efficiency of labeling cells using two commercially available FDA-approved agents: ferumoxide, a suspension of dextran-coated SPIO used as an MRI contrast agent and protamine sulfate used ex vivo as a cationic transfection agent to evaluate the use of clinical 1.5 Tesla magnetic resonance imaging equipment in showing the in vivo homing of iron oxide-labeled human CD34+ cells in irradiated mouse. After labeling human Hematopoietic (CD34+) stem cells with ferumoxide-protamine sulfate complex (FE-Pro), cellular toxicity, functional capacity and quantitative cellular iron incorporation were determined. FE-Pro labeled cells demonstrated neither short or long-term toxicity nor changes in colonogenic assay of the stem cells and their phenotype when compared with unlabeled cells. Efficient labeling with FE-Pro was observed with iron content per cell varying between 1.91 +/- 0.1 pg for CD34+ cells with 100% of cells labeled. After irradiation, Female Balb/c mice underwent MR imaging before and 12, 24, 48 and 72 h after intravenous injection of 0.5-1.5 x 10(7) labeled CD34+ cells. A significant decrease in MR signal intensity was observed in bone marrow at 24 and 48 h after injection. Our observations confirm that efficient labeling of cells with appropriate contrast agents should facilitate the translation of this method to clinical trials for evaluating the trafficking of infused or transplanted cells by MR Imaging.