Quantum Dots Do Not Affect the Behaviour of Mouse Embryonic Stem Cells and Kidney Stem Cells and Are Suitable for Short-Term Tracking

Abstract

Quantum dots (QDs) are small nanocrystals widely used for labelling cells in order to enable cell tracking in complex environments in vitro, ex vivo and in vivo. They present many advantages over traditional fluorescent markers as they are resistant to photobleaching and have narrow emission spectra. Although QDs have been used effectively in cell tracking applications, their suitability has been questioned by reports showing they can affect stem cell behaviour and can be transferred to neighbouring cells. Using a variety of cellular and molecular biology techniques, we have investigated the effect of QDs on the proliferation and differentiation potential of two stem cell types: mouse embryonic stem cells and tissue-specific stem cells derived from mouse kidney. We have also tested if QDs released from living or dead cells can be taken up by neighbouring cells, and we have determined if QDs affect the degree of cell-cell fusion; this information is critical in order to assess the suitability of QDs for stem cell tracking. We show here that QDs have no effect on the viability, proliferation or differentiation potential of the two stem cell types. Furthermore, we show that the extent of transfer of QDs to neighbouring cells is <4%, and that QDs do not increase the degree of cell-cell fusion. However, although the QDs have a high labelling efficiency (>85%), they are rapidly depleted from both stem cell populations. Taken together, our results suggest that QDs are effective cell labelling probes that are suitable for short-term stem cell tracking.

Quantum Dots Do Not Alter the Differentiation Potential of Pancreatic Stem Cells and Are Distributed Randomly among Daughter Cells

“…As the growth curves of both cell populations were nearly congruent, no apparent deleterious effects could be discovered for the labeled cell population. Overall QDs seem to be well tolerated by proliferating cells and do not interfere with cell division, which could be also evidenced for red emitting QDs by other working groups [24, 32, 35, 37]. Owing to the special properties of stem cell populations, it is of major importance to warrant unaffected gene and protein expression and to characterize their multipotent differentiation potential with respect to any QD induced changes.…”

“…Their advantageous properties offered also many strategies in vivo including labeling of zebrafish embryos [33] or Xenopus embryos [34]. Whereas several reports suggest that QDs are non-toxic [26, 34, 35] some groups reveal possible cytotoxic or aberrant effects of QDs depending on their size, coating and physiochemical properties [29, 36, 37]. For example, it has been shown that human bone marrow mesenchymal stem cells were affected in their osteogenic differentiation in vitro by CdSe/ZnS quantum dot labels [36].…”

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

“…QDs have already been employed to track MSCs in regenerative or cancer therapies due to their superior in vitro cell tracking capability compared to commercial cell trackers. 25 The large surface area of nanoparticles allows the attachment of multiple biologically active molecules, such as proteins, drugs, photosensitizers, and/or antibodies. 24 Thus, QDs could combine a cell-imaging probe and a tumor-targeting agent in one platform.…”

“…Although it has been noted that QDs might leak from intact stem cells, 56,58,77 it was also reported that QD-labeled cells retain bright QD PL for a few weeks and do not transfer nanoparticles to adjacent cells and host tissues. 25,78,79 Such disagreements might be explained by different QD surface charges, as positively charged nanoparticles were used in most studies that showed QD leakage from cells, 56,77 while negatively charged nanoparticles were retained inside the cells better. 78,79 Our previous in vitro studies showed that QD PL decreases by 30% after the first 24 h most probably due to some degradation in lysosomes and does not change after additional 24 hours.…”

Quantum dots induce heat shock-related cytotoxicity at intracellular environment

“…However, the most useful QDs contain toxic elements, mostly cadmium. Although QDs injection in animals does not trigger nefarious events over a limited timeline (up to a few mo) (Rak-Raszewska et al 2012), concerns have risen about the long-term cytotoxicity of QDs as a consequence of slow degradation of the shell built around the CdSe core upon exposure to the biological milieu (Derfus et al 2004;Michalet et al 2005;Cho et al 2007;Winnik and Maysinger 2013).…”