Function of mesenchymal stem cells following loading of gold nanotracers

Abstract

Background: Stem cells can differentiate into multiple cell types, and therefore can be used for cellular therapies, including tissue repair. However, the participation of stem cells in tissue repair and neovascularization is not well understood. Therefore, implementing a noninvasive, long-term imaging technique to track stem cells in vivo is needed to obtain a better understanding of the wound healing response. Generally, we are interested in developing an imaging approach to track mesenchymal stem cells (MSCs) in vivo after delivery via a polyethylene glycol modified fibrin matrix (PEGylated fibrin matrix) using MSCs loaded with gold nanoparticles as nanotracers. The objective of the current study was to assess the effects of loading MSCs with gold nanoparticles on cellular function. Methods: In this study, we utilized various gold nanoparticle formulations by varying size and surface coatings and assessed the efficiency of cell labeling using darkfield microscopy. We hypothesized that loading cells with gold nanotracers would not significantly alter cell function due to the inert and biocompatible characteristics of gold. The effect of nanoparticle loading on cell viability and cytotoxicity was analyzed using a LIVE/DEAD stain and an MTT assay. The ability of MSCs to differentiate into adipocytes and osteocytes after nanoparticle loading was also examined. In addition, nanoparticle loading and retention over time was assessed using inductively coupled plasma mass spectrometry (ICP-MS). Conclusion: Our results demonstrate that loading MSCs with gold nanotracers does not alter cell function and, based on the ICP-MS results, long-term imaging and tracking of MSCs is feasible. These findings strengthen the possibility of imaging MSCs in vivo, such as with optical or photoacoustic imaging, to understand better the participation and role of MSCs in neovascularization.

Reversing chemoresistance of malignant glioma stem cells using gold nanoparticles

“…Generally, gold nanoparticles have been reported to have good biocompatibility with nonstem cells, but with effects dependent upon the particular cell line used in the experiment. [32][33][34] Moreover, the surface chemistry, 35 size, 35 and concentration have been shown to affect the internalization mechanism for such nanomaterials. 36 The surface modifiers used to stabilize gold nanoparticles include a range of anionic, cationic, and neutral groups, such as citrate, amine, and glucose.…”

Nanoparticles and their potential for application in bone

“…The promising fields for MSC application range from promoting bone regeneration 19,20 to improving fracture healing. [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.…”

“…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.…”

“…102 In contrast, other metallic particles, such as gold nanotracers, did not affect MSC differentiation into the osteogenic and adipogenic lineages. 28 Similarly, polymeric phosphonate-functionalized particles, which exhibited excellent binding properties to metallic surfaces such as titanium dioxide, 103 were investigated with regard to their effect on MSC differentiation. Qualitative characteristic staining as well as comprehensive quantitative analyses of marker gene expression for the osteogenic, adipogenic, and chondrogenic lineages revealed no detrimental effect arising from the phosphonate-functionalized particles.…”

Stem cell tracking using iron oxide nanoparticles

“…However, there has been evidence to suggest that endocytic lifecycles can be affected due to nanoparticles residing in endosomes. 45 Studies were undertaken, which showed that it is the iron itself within the SPION that caused impairment in chondrogenic differentiation, as opposed to any transfection factors that were present; [46][47][48] however, other research shows that it is the transfection agent, PLL, that causes this effect on differentiation (for more toxicity information, see Table 2). The application of SPIONs in medicine brings a new dimension into monitoring stem cells in vitro and in vivo.…”