Bifunctional Magnetic Silica Nanoparticles for Highly Efficient Human Stem Cell Labeling

Abstract

A superparamagnetic iron oxide (SPIO) nanoparticle is emerging as an ideal probe for noninvasive cell tracking. However, its low intracellular labeling efficiency has limited the potential usage and has evoked great interest in developing new labeling strategies. We have developed fluorescein isothiocyanate (FITC)-incorporated silica-coated core-shell SPIO nanoparticles, SPIO@SiO2(FITC), with diameters of 50 nm, as a bifunctionally magnetic vector that can efficiently label human mesenchymal stem cells (hMSCs), via clathrin- and actin-dependent endocytosis with subsequent intracellular localization in late endosomes/lysosomes. The uptake process displays a time- and dose-dependent behavior. In our system, SPIO@SiO2(FITC) nanoparticles induce sufficient cell MRI contrast at an incubation dosage as low as 0.5 microg of iron/mL of culture medium with 1.2x105 hMSCs, and the in vitro detection threshold of cell number is about 1x104 cells. Furthermore, 1.2x105 labeled cells can also be MRI-detected in a subcutaneous model in vivo. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation capacities into adipocytes and osteocytes which can still be readily MRI detected. This is the first report that hMSCs can be efficiently labeled with MRI contrast nanoparticles and can be monitored in vitro and in vivo with a clinical 1.5-T MRI imager under low incubation concentration of iron oxide, short incubation time, and low detection cell numbers at the same time.

Magnetic Nanoparticles: Its Effect on Cellular Behaviour and Potential Applications

“…The mechanism of MNPs uptake by different kinds of stem cells are not fully investigated but recent study shows endocytosis by clathrin receptor is one of the mechanisms (Huang et al, 2005;Lu et al, 2007). These study shows inhibitor of clathrin receptor, phenylarsine oxide, can block the ingestion of mesoporous iron oxide nanoparticles into human mesenchymal stem cells.…”

Nanoparticles and their potential for application in bone

“…[21][22][23][24] To monitor these processes, MSCs have been labeled with diverse nanoparticles, such as quantum dots, which are small semiconductor nanocrystals, 25,26 fluorescence-labeled mesoporous silica nanoparticles, 27 gold nanoparticles, 28 or superparamagnetic iron oxide (SPIO) nanoparticles. [29][30][31] Several types of SPIO nanoparticles have already been clinically approved for use as contrast agents in MRI, eg, of bowel or liver. 32 It should be noted that bone represents a formidable target organ, which poses a particular challenge with regard to cell labeling, due to its high mineralization grade, making the visualization of labeled cells in MRI difficult.…”

“…With respect to bone cells, and particularly MSCs, the particles ideally should not compromise the differentiation potential. In vitro analyses of MSC differentiation capacity in the presence of nanoparticles demonstrated the innocuousness of several SPIO nanoparticles, [29][30][31]33 as well as of certain gold nanoparticles 28 that were optimized for efficient MSC labeling and MRI visualization. As the MSC differentiation potential in vitro does not necessarily correlate with the in vivo situation, a study investigating the stemness of MSCs exposed to SPIO nanoparticles went one step further by verifying the differentiation capacity in vivo based on ossicle formation by labeled human MSCs in immunocompromised mice.…”

Surface modification and cellular uptake evaluation of Au-coated Ni 80 Fe 20 nanodiscs for biomedical applications

“…However, recent developments in this field have brought an increased interest in the synthesis and characterization of new types of magnetic nanoparticles. In particular, the ability to control size, shape and composition of magnetic nanoparticles can provide flexibility for biomedical applications, such as DNA separation, cell labelling, magnetic resonance imaging, drug delivery and magnetic hyperthermia [3][4][5][6].…”