Biology Reference
In-Depth Information
predicted to have therapeutic roles in treating ischemic conditions [
100
] . The vesi-
cles can be used as natural targeted delivery vehicles if the secreting cells are geneti-
cally modified to express modified exosomal membrane proteins that bind to specific
receptors on the targeted cells [
101
]. After the targeted exosomes have been isolated
from these cells, they can then be loaded with specific RNAs by electroporation.
Such exosomes were successfully used to deliver siRNA to the brain in vivo where
the target BACE1, a protein involved in Parkinson's disease, was silenced. We fore-
see that such vesicles will play a great role in future regenerative medicine as deliv-
ery vehicles for siRNA and miRNA modulators. However, while the direct delivery
of miRNA using such vesicles has been demonstrated, we have yet to see whether
such vesicles can be successfully combined with scaffolds and cell therapy.
3.5
Future Perspectives
The real advantage of miRNA-based regenerative medicine lies in the flexibility
offered by the multitude of cellular functions that can be modulated once a miRNA
delivery system has been devised for a particular application. Our group has, for
example, used one siRNA delivery system to enhance both adipogenic and osteo-
genic differentiation on a scaffold [
25
]. MicroRNAs, however, would probably per-
form even better for this purpose than siRNAs since they target multiple genes and
are “optimised” by nature for purposes such as differentiation. Numerous miRNAs
have been characterised well enough for these purposes already, and the continued
elucidation of endogenous and exogenous miRNA functions in tissue regeneration
and repair will undoubtedly expand the potential miRNA can have in regenerative
medicine. Currently, high-throughput methods for characterising miRNA expres-
sion, such as microarrays [
5
] and next generation sequencing [
29
] , are providing
detailed descriptions of the presence and role various miRNAs play in differentia-
tion events. Ideally, such studies would be designed to provide us with the temporal
and spatial information needed to grow complex tissues: For example, by detailing
the sequential expression of miRNAs at successive differentiation stages so that we
can place those miRNAs into scaffolds that release them in the correct order or
by analysing different differentiation pathways in parallel studies to reveal which
miRNAs that may be placed in spatially different parts of an implant generate tis-
sues with multiple cell types.
At the same time, scaffold and implant development must take place to ensure
that such detailed biological knowledge can be mimicked artificially. Continual
research on how drugs interact with implants is necessary so that different methods
of drug incorporation can be devised that give controllable release rates. This may
include devising polymers or scaffold architectures with different bulk degradation
rates or tailoring the delivery systems to bind the implants with different degrees of
affinity and, thus, release rates. Alternatively, one could envisage a scaffold contain-
ing stimuli-responsive polymers where an externally applied stimulus such as heat
or ultrasound triggers the release of drugs. Such a scaffold could be used to accom-
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