| The development of the nanotechnology enables special tailoring the functional properties of nanoparticles for biomedical and diagnostic applications. In this dissertation, cell magnetic nanoparticle tagging and cell magnetophoresis are investigated for applications in the areas of cellular therapy and imaging. Enrichment of blood progenitor cells with concomitant depletion of unwanted cells improves patient recovery in autologous and allogeneic stem cell transplantations. In this study, a quadrupole magnetic flow sorter (QMS), a flow-through magnetophoretic device, was evaluated using two strategies for the enrichment of blood progenitors from the clinical leukapheresis product samples. In the positive selection, seven commercial CD34+ progenitor cell-labeling reagents were evaluated quantitatively for the best performance through analysis of magnetophoresis process using cell tracking velocimetry (CTV). The reagent that produced the highest magnetophoretic mobility was selected for positive selection experiments (n=22). The CD34+ cells were isolated with a purity of 60%-96%, a recovery of 18%-60% and an enrichment rate of 12-169. In the negative depletion, a tetrameric antibody cocktail (TAC) and magnetic colloid against non-progenitor leukocytes was evaluated and used for negative progenitor enrichment experiments (n=23). The progenitor cells were isolated with a purity of 30%-85%, a recovery of 49%-84% and an enrichment rate of 8-104. Negative cell retention, a critical issue for the QMS process scale-up, was also investigated using a full-factorial experimental design, followed by a regression analysis of the cell sorting process. The intracellular magnetic particle tagging has been recently proposed for in-vivo magnetic resonance imaging (MRI) tracking of magnetically labeled progenitor cells. In this dissertation, the magnetophoretic motion analysis is applied to quantitate the cellular particle uptake and intracellular iron content. The intracellular superparamagnetic iron oxide (SPIO) nanoparticle uptake was facilitated by transfection agents (TAs) in live cells. The uptake was measured quantitatively from magnetophoresis by CTV. Seven different TAs-SPIO complexes based on dendrimer, lipid and polyethylenimine compounds applied to mesenchymal and hematopoietic progenitor cells and cardiac fibroblasts were evaluated. The results showed significant labeling differences, important for reagent selection as an MRI intracellular contrast. |
