24
cases MRI detection requires clusters of thousands of labeled cells [ 47 ], and this
becomes problematic as extensive in vivo-migration of SPIOs labelled cells occurs
and density of cells in a given area is reduced over time. Long-term observation of
SPIOs labelled stem cells may also be limited because of dilution by cell division
[ 2 ]. Thus further research and eventual standardization of SPIOs is needed before
the marked potential in becoming a routine method of stem cell labeling and in vivo
tracking via MRI is brought to realization.
2.4.2 Quantum Dots
Quantum dots are spherically shaped semiconductor light-emitting crystals with a
diameter of approximately 2–10 nm (Fig. 2.4). They have the ability to convert short
wavelength light into nearly any color in the visible spectrum with a high efficiency
[ 53 ]. The general public may recognize quantum dots as their properties are cur-
rently exploited in the electronics industry in making brighter television screens.
Quantum dots have a solid long-term photo-stability and durability which makes
them ideal for live-cell imaging and dynamics studies. They can also concurrently
tag multiple inter- and intracellular components for time ranging from seconds to
months. Thanks to the narrow emission spectrum and broad excitation spectrum of
quantum dots, several cell components can be visualized with fluorescent micros-
copy by using different colored quantum dots in vivo [ 2 , 54 ]. Based on these favor-
able properties, quantum dots have been used for almost two decades for bio-imaging
applications, in particular, to label different cell lines for both in vitro and in vivo
studies [ 55 , 56 ]. Common methods used for an efficient intracellular delivery of
quantum dots are microinjection, electroporation, lipid based transduction, and
peptide-mediated delivery [ 16 ].
Quantum dots consist of elements such as indium phosphamide and cadmium
telluride, the latter being extremely toxic to humans. Investigators have aimed to
mitigate this problem by coating the cadmium core of a quantum dot with a zinc
sulfide buffer layer or manufacturing cadmium-free quantum dots [ 57 – 59 ]. In
experimental in vitro studies done in human embryonic and mesenchymal stem
cells, quantum dots have been shown to be mostly safe without major interferences
in stem cell morphology, viability, proliferation or differentiation [ 60 – 62 ]. In vivo
preclinical studies have shown that quantum dot-labeled stem cells can be tracked
in the mammalian nervous system (neural stem cells and neural progenitor cells)
[ 63 ], cardiac tissue (mesenchymal stem cells) [ 64 ] and in angiogenesis (embryonic
stem cells) [ 65 ].
Quantum dots are most appropriate for fluorescence imaging, and the main chal-
lenge is light scattering that makes it difficult to locate the labelled cells in 3D and
to estimate cell survival in quantity [ 66 ]. Quantum dots are suitable for in vivo
imaging with: fluorescence (light/confocal/two-photon microscopy).
H.A. Jensen et al.