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detection as deep as 10 cm. Therefore, NIR QDs may soon prove useful for
noninvasive stem cell tracking.
Another approach toward using QDs for noninvasive stem cell tracking
is to capitalize on their inherent features and use existing technologies for
detection. Both the core of the QD and the passivating shell contain metal
ions (cadmium and zinc, respectively). Metals are radiopaque and can, there-
fore, be imaged using X-ray technology. Traditional X-rays are too large to
interfere with nano- or microscale metals, but it might be possible to use
micro-computed tomography (µCT) scanning to image QDs in vivo . Based
on theoretical data* and preliminary experiments in our laboratory, we have
found that µCT can detect QD-labeled stem cells in both explanted tissue
samples and in living animals. Still, further experiments will be necessary
before this approach can be applied in large animals.
Finally, it may also soon be possible to track QD-labeled stem cells nonin-
vasively using MRI. Several laboratories have attempted to create paramag-
netic QDs by coating the particles with designer lipids (Mulder et al . 2006)
or doping with metals such as manganese (Yong 2009). QDs may represent a
more favorable option for this approach than SPIOs as they will likely load
more easily into the cells and avoid the potential problem of interfering with
differentiation. While this technology is not yet optimized, paramagnetic
QDs should permit noninvasive detection of populations of labeled stem
cells in deep tissue and the ability to identify single cells via QD fluorescence
in histological sections of explanted tissue samples without secondary stain-
ing (Bakalova and Zheler 2007).
14.5 Summary and Limitations
QDs appear to satisfy many, but not all, of the criteria of an “ideal” tracking
agent as listed in Section 14.1. They can be loaded into cells without genetic
or mechanical perturbation, and once inside the cell they are biocompatible,
safe, and nontoxic; they do not interfere with cell proliferation or differen-
tiation or transfer to adjacent (unlabeled) cells. In at least the case of label-
ing human mesenchymal stem cells, nearly 100% of the cells uniformly take
up QDs (Rosen et al . 2007). QD-labeled cells can be delivered to animals,
subsequently identified in the host tissue with single-cell resolution (in his-
tological sections of explanted tissue), and the number of cells can be quanti-
ied. However, there are some important limitations to their usage. First, as
with any exogenous label inside a cell, the threshold of detection is based in
part on the dilution of that label over multiple cell divisions. In our hands,
* Data are based primarily on the difference in density between QD-labeled stem cells and
surrounding mammalian tissue.
 
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