DNA- or siRNA-loaded NPs immobilized on the surface-coated ECM may also
allow the controlled release of DNA, leading to long-term expression of the desired
protein for enhanced differentiation [122]. Hosseinkhani et al. [48] observed that
simple mixing of plasmid DNA (encoding BMP-2) and acetylated PEI solutions
and their encapsulation within scaffolds (collagen sponges reinforced by
incorporating of poly(glycolic acid) fibres) led to homogenous bone formation
throughout the sponges. This strategy could be of particular importance for delivery
of siRNAs, which are known to have a short half-life. Furthermore, adhering NPs
containing different DNAs or siRNAs into nanostructured 3D scaffolds could allow
spatial retention of the DNA or siRNA within nanopores until their cellular
delivery. Different NPs localized to spatially distinct locations within a single
implant might allow two different tissue types to develop in controllable areas of
an implant. Thus, complex tissues and organs can be engineered by the in situ
development of multiple cell types guided by spatially restricted NPs [120].
4.3 Stem Cells as Carriers of NPs or DNA NPs
NPs, loaded with or without genes, can also be used to track the cellular distribution, differentiation and fate of stem cells after their in vivo transplantation. NPs
such as quantum dots, MNPs and magnetic carbon nanotubes can be easily loaded
into stem cells and visualized by imaging techniques such as magnetic resonance
imaging (MRI) or fluorescent imaging for monitoring the fate of the transplanted
stem cells. These NPs have better photostability and longevity than chemical dyes
and, hence, are advantageous. Ruan et al. [118] labelled iPS cells with MNPs and
found them suitable for long-term observation and tracking of stem cells through
fluorescent microscopy and MRI [118]. Alternatively, fluorescent markers such as
EGFP, YFP, CFP, RFP, etc. can be introduced into the stem cells by NP-based gene
delivery methods for tracking the fate of the transplanted cells [56].
Because stem cells have the intrinsic ability to “home” into transplanted organs,
they can also be used as a delivery vehicle to deliver therapeutic genes and/or track
NPs into a target organ. Tang et al. [123] introduced SPION into therapeutic MSCs
to act as contrast enhancers for tracking the transplanted cells by MRI. Kim et al.
[124] used SPION to transfer genes into MSCs and found the method to be safe and
effective. However, SPION/PLL labelling of C17.2 neural stem cells was shown to
result in altered gene expression as an early cellular response and, therefore, further
improvement may be necessary [6].
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