Biomedical Engineering Reference
In-Depth Information
impacted cell viability and proliferation, yet positively impacted differentiation in this study.
The internalization and perinuclear accumulation of PLGA nanoparticles within hESC
colonies and aggregated hESCs forming embryoid bodies showed no adverse effects on
cell viability or proliferation in cells that contained nanoparticles.
Gwak
et al
. [36] developed PLGA particles as nanocarriers for gene delivery to human
cord blood-derived MSCs. A comparison of cytotoxicity and long-term transgene expres-
sion between PLGA nanocarriers and PEI showed that PLGA were significantly less
cytotoxic and had higher transgene expression
in vitro
for a longer duration (21 days) than
PEI. The authors have stated that PLGA nanoparticles provided a higher potential as gene
delivery carriers for use in gene therapy for diseases in which a long-term therapeutic gene
expression regimen is necessary.
Park
et al
. [37] investigated a PEI-modified PLGA nanoparticle to assess the ability of
four genes (transcription factor) polyplexed with nanocarriers that were delivered intracel-
lularly in hMSCs. For polyplexed genes with PEI-PLGA nanoparticles, the obtained
transfection efficiency was approximately 80% and led to a significant increase in chondro-
genesis
in vitro
. The cell-uptake ability of the gene-loaded nanocarriers was enhanced for
both
in vitro
and
in vivo
culture systems, including hMSCs. The same group, in another
study [38], used PLGA nanoparticles as gene carriers to mediate the transfer of the SOX9
gene in hMSCs. The nanocarriers that were complexed with high levels of SOX9 plasmid
DNA allowed robust gene expression in hMSCs both
in vitro
and
in vivo
, and induced
chondrogenesis. In an additional work [39], they reported inhibition of expression of
unnecessary genes and enhanced expression of specific genes involved in hMSC differen-
tiation by the simultaneous application of siRNA and plasmid DNA that were incorpo-
rated into cationic PEI coated on PLGA nanoparticles as co-delivery factors. Use of
nanocarriers has also allowed for simultaneous introduction of a DNA vector and siRNA,
which enhances efficient differentiation. After transfection the percentage of GFP-
expressing hMSCs decreased from 25.35 to 3.7% with GFP-DNA/PLGA or GFP-siRNA/
PLGA, whereas GFP-DNA/PLGA and scramble siRNA (MOCK)/PLGA had no adverse
effect on GFP expression.
Chitosan
Chitosan is a nontoxic, biodegradable, natural polysaccharide consisting of repeating units
of N-acetyl-glucosamine and glucosamine, the proportions of which determine the degree
of deacetylation and the polymer's properties of solubility, hydrophobicity, and the ability
to interact with polyanions [7].
Chitosan can condense DNA and protect it against nuclease degradation. Furthermore,
CS nanoparticles are stable during storage and their preparation does not require organic
solvents, which minimizes possible damage to DNA during complexation. Thus, it is a good
candidate as a nonviral gene delivery nanocarrier. Generally, a low molecular weight, highly
deacetylated CS results in small sized nanoparticles with highly condensed DNA [40].
For the first time, Corsi
et al
. [41] synthesized a cationic CS-DNA plasmid complex
to evaluate the potential for CS to develop a nonviral gene-delivery nanocarrier in a
variety of cell types, including hMSCs. These CS-DNA nanoparticles were shown to
have lower cytotoxicity than lipoplexes and gene delivery efficiency was dependent on
the cell type.
Oliveira
et al
. [42] conducted research on the impact of combining dexamethasone (Dex)
loaded carboxymethylchitosan/poly(amidoamine), or (Dex-loaded CMCht/PAMAM),
nanoparticles and both hydroxyapatite and starch-polycaprolactone scaffolds (three-dimensional
system) on the
in vitro
expansion and osteogenic differentiation of rat bone-marrow stromal
