Biomedical Engineering Reference
In-Depth Information
4.7 Future Trends
Although human gene therapy has been a rapidly growing field in recent years,
several obstacles still exist, among which the lack of effective and safe delivery
vectors suitable for clinical use is still the greatest challenge.
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Based on new
understanding of molecular biology and medicine, therapeutic nonviral vectors
for cancer gene therapy will be improved for greater safety and efficacy.
Currently, we have to confront challenges associated with cell targeting
specificity, gene transfer efficiency, gene expression regulation, and vector
safety. Hence, the successful nonviral vectors for future gene therapy must be
multifunctional systems, and will be more efficient in targeting and
transfection. Additionally, they should be biocompatible and biodegradable
to prevent vector-induced toxicities and the accumulation of vector compo-
nents in the host. Accordingly, more efforts should be made in order to
facilitate DNA release where LMW polymers are crosslinked or linearly linked
together by degradable linkages to form a HMW polymer that can eventually
degrade into its LMW components. Various new ideas have been proposed
and reported, helping us estimate future trends in development of nonviral
gene delivery systems.
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4.7.1 Stem Cell Transfection
Stem cells are the precursors for embryonic development as well as adult tissue
regeneration. As such, stem cell therapy holds great promise for the field of
regenerative medicine. In the past decade, a number of studies have shown that
genetic modification of stem cells can improve their therapeutic potential in
vivo as well as allow for their monitoring via the introduction of reporter genes.
Research on nonviral vector-mediated stem cell gene transfection has become a
hotspot.
Ramasubramanian et al. reported a combinatorial nonviral gene delivery
platform that targets both inductive and suppressive genes for promoting
osteogenic differentiation in human adipose-derived stem cells (hADSCs).
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They found that co-delivery of poly(b-amino esters)/BMP2 DNA complexes
and lipidoid/siGNAS complexes (or lipidoid/siNoggin complexes) significantly
accelerated the hADSC differentiation towards osteogenic differentiation, with
marked increase in bone marker expression and mineralization.
Roger et al. demonstrated that marrow-isolated adult multilineage inducible
(MIAMI) cells could serve as cellular carriers for NPs in brain tumors.
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Two
types of NPs loaded with coumarin-6 were investigated: poly(lactic acid) NPs
(PLA-NPs) and lipid nanocapsules. The results showed that these NPs could
be efficiently internalized into MSCs while cell viability and differentiation
were not affected. Furthermore, these NP-loaded cells were able to migrate
toward an experimental human glioma model. These data suggested that
MSCs could serve as cellular carriers for NPs in brain tumors.
