1. Uptake and distribution of carboxylated quantum dots in human mesenchymal stem cells: cell growing density matters
- Author
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Ricardas Rotomskis, Marijus Pleckaitis, Simona Steponkiene, Vitalijus Karabanovas, Zivile Gudleviciene, Marina Juraleviciute, and Gabrielis Kundrotas
- Subjects
lcsh:Medical technology ,Time Factors ,Cell Survival ,lcsh:Biotechnology ,Biomedical Engineering ,Carboxylic Acids ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,02 engineering and technology ,Filopodia-like structures ,010402 general chemistry ,01 natural sciences ,Applied Microbiology and Biotechnology ,Regenerative medicine ,Fluorescence imaging ,Cell therapy ,Extracellular matrix ,Tissue engineering ,Cell Movement ,Labeling ,lcsh:TP248.13-248.65 ,medicine ,Extracellular ,mesenchymal stem cells ,filopodia-like structures ,extracellular matrix ,labeling ,quantum dots ,fluorescence imaging ,fluorescence-lifetime imaging microscopy ,Humans ,Fluorescent Dyes ,Staining and Labeling ,Chemistry ,Quantum dots ,Research ,Mesenchymal stem cell ,Optical Imaging ,technology, industry, and agriculture ,Biological Transport ,Mesenchymal Stem Cells ,Fluorescence-lifetime imaging microscopy ,021001 nanoscience & nanotechnology ,equipment and supplies ,3. Good health ,0104 chemical sciences ,medicine.anatomical_structure ,Endocytic vesicle ,lcsh:R855-855.5 ,Biophysics ,Molecular Medicine ,Bone marrow ,0210 nano-technology - Abstract
Background Human mesenchymal stem cells (MSCs) have drawn much attention in the field of regenerative medicine for their immunomodulatory and anti-inflammatory effects. MSCs possess specific tumor-oriented migration and incorporation highlighting the potential for MSCs to be used as an ideal carrier for anticancer agents. Bone marrow is the main source of MSCs for clinical applications. MSCs tracking in vivo is a critical component of the safety and efficacy evaluation of therapeutic cell products; therefore, cells must be labeled with contrast agents to enable visualization of the MSCs migration in vivo. Due to their unique properties, quantum dots (QDs) are emerging as optimal tools in long-term MSC optical imaging applications. The aim of this study was to investigate the uptake dynamics, cytotoxity, subcellular and extracellular distribution of non-targeted carboxylated quantum dots in human bone marrow MSCs at different cell growing densities. Results QDs had no negative impact on MSC viability throughout the experiment and accumulated in all observed cells efficiently; however, in some MSCs QDs induced formation of lipid droplets. At low cell growing densities QDs distribute within MSCs cytoplasm already after 1 h of incubation reaching saturation after 6 h. After 24 h QDs localize mainly in the perinuclear region of the cells in endosomes. Interestingly, in more confluent culture QDs localize mostly outside MSCs. QDs abundantly mark MSC long filopodia-like structures attaching neighboring cells. At high cell density cultivation, we for the first time demonstrated that carboxylated QDs localize in human bone marrow MSC extracellular matrix. Moreover, we observed that average photoluminescence lifetime of QDs distributed in extracellular matrix are longer than lifetimes of QDs entrapped in endocytic vesicles; thus, for the first time showing the possibility to identify and distinguish localization of QDs in various extracellular and intracellular structures using fluorescence-lifetime imaging microscopy without additional staining assays. Conclusion Carboxylated QDs can be used as nonspecific and effective dye for staining of human bone marrow MSCs and their specific extracellular structures. These results are promising in fundamental stem cell biology as well as in cellular therapy, anticancer drug delivery and tissue engineering. Electronic supplementary material The online version of this article (10.1186/s12951-019-0470-6) contains supplementary material, which is available to authorized users.
- Published
- 2019