Biomedical Engineering Reference
In-Depth Information
regulating gene responsible for proliferation, differentiation, and migration in hMSCs. In
addition, it was found to be upregulated during myogenic differentiation
in vitro
and induced
during the regenerative phase after ischemia.
In another work [48] the same group improved the transfection of hMSCs by an intracel-
lular delivery of pDNA through a magnetic polyplex. They verified the possibility of substi-
tuting the pDNA/PEI delivery system by PEI-condensed pDNA incorporated with MNP.
Indeed this new delivery system was fabricated and applied without application of a
magnetic force considering the biotin-streptavidin interactions that could provide higher
transfection effectiveness. The results of the study showed significantly more efficient
capacity of PEI/DNA/MNPs to release pDNA than traditional pDNA/PEI alone.
Polymer-Silica Hybrid
An unsolved problem for the use of SiNP in nonviral gene delivery is the potential toxicity
of these particles. In order to overcome this problem, coating of biomaterials onto the
nanoparticle surfaces is an essential step. Unfortunately, the cytotoxicity of SiNP increases
with increasing dose, exposure duration, and metabolic activity of the cell.
Park
et al
. [60] prepared PEI/pDNA coated SiNP for nonviral gene delivery into stem
cells, which stressed the ability of the system to facilitate high levels of gene expression. By
polyplexing with PEI, there was enhanced ability of nanoparticles for cell-uptake in both
in
vitro
and
in vivo
culture systems. The authors reported that 75% of hMSCs showed uptake
for this nanocarrier. Although PEI has been previously identified as a potential candidate
for gene delivery systems, PEI alone did not appear to sufficiently bind to specific genes.
However, PEI complexed with nanoparticles seemed to have the necessary gene-binding
capacity. Thus, PEI/pDNA was completely complexed by ionic binding with negatively
charged nanoparticles. The result indicated that probably PEI alone did not have the capacity
to deliver genes into stem cells since the stem cells proved unviable at high doses of PEI. This
study showed that the PEI-mediated gene nanocarriers penetrated into the cell membrane
and facilitated gene delivery.
Conclusions
For delivery, numerous nanoengineered carriers, known as nanoparticles, with variable
compositions are generally used as intracellular carriers to control stem-cell fate. The nano-
engineered carriers are a promising technique to convert laboratory results into clinically
viable applications with stem cells. The size, shape, charge, and surface chemistry of nano-
carriers are the main factors that govern cellular uptake and the process of cellular delivery.
Modified stem cells show superior characteristics of specific tissue differentiation, direc-
tional migration, and resistance to apoptosis.
Despite remarkable enhancement, nanoparticulated delivery systems still suffer from low
transfection efficiency. Several features are desirable in the development of delivery
approaches of nanoparticles for therapeutic purposes - the ability to deliver sufficient
amounts of nanoscale materials intracellular to mediate agent delivery of the desired
function; the ability to deliver nanoparticles in a specific, controlled manner to only the
targeted cell population; and elicitation of minimal cytotoxicity. Further research is needed
for tailoring the size, content and surface properties as well as several problems regarding
their fate, toxicity and safety must be addressed. Lastly, nanoengineered delivery offers new
opportunities for transgenesis that should be investigated.
