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Introduction 19F based stem-cell labelling is attractive, since it may enable long-term studies of cellular migration provided sufficient detection sensitivity can be achieved and has no background signal. Several 19F based compounds are based on a cocktail of approved pharmaceutical compounds, that facilitates translationonal studies. 19F-PLGA: poly(D,L-lactide-co-glycolide) has successfully been used for tracking of dendritic cells and has clinical research approval [1]. Methods 19F PLGA nanoparticles (19F PLGA NP) of various compositions, with and without surface modification were prepared by encapsulation of of perfluoro-15-crown-5-ether and by optical probes (carboxyfluorescein). The nanoparticle size was determined by DLS light scattering. Human mesenchymal stem cells (hMSC) were incubated in a solution containing a maximum of 4mg of the nanoparticles for a 1-3 days. The influence of 19F-PLGA-NP labelling on the following parameters was investigated: proliferation kinetics, colony generation, adhesion, surface migration, and presence of stem-cell markers. Fluorescence microscopy was used to verify cellular uptake of the compound, while cell loading was determined by MR spectroscopy and referencing to tri-fluoroacetic acid at 7T. The longitudinal relaxation time of the free nanoparticles and after hMSC labelling was determined at 7T. MRI sequence optimization was performed by simulation of the expected MR signal in Matlab [2] and labelled cells were measured either as a pellet or as an agarose suspension. Results Without surface modification, no uptake in hMSC occurred (0.01x1012 19F/cell). while the cell-load increased after surface modification and optimization of the loading protocol (0.29-1.16x1012 19F/cell). The size of the nanoparticles was 306nm, with a PDI of 0.16. No significant influence of 19F-PLGA-NPs on the cells was observed after achieving a cell loading of 1.16x1012 19F/cell. The T1 time of the 19F-PLGA-NP decreased from 1090 to 790ms after loading. In vitro, the T2 time was 590ms. The MRI detection limit with a cell load of 0.4x1012 19F/cell in a 2h scan was 20.000 cells (pellet) or 10.000 cells per microliter (suspension). Conclusions Besides optimization of the imaging protocol, a significant increase in MRI sensitivity can be achieved through improving the cell-load. The 19F-PLGA-NP did not significantly alter the properties of hMSC. In vivo studies of 19F-PLGA-NP labelled hMSC are under way to verify the utility of this technique in a pre-clinical setting.