Biology Reference
In-Depth Information
3.1
Introduction
Regenerative medicine aims to guide and promote the repair of damaged tissues or,
if needed, replace them with living tissues created through tissue engineering.
MicroRNAs (miRNAs) are a continually expanding class of endogenously expressed
non-coding RNAs that, through a phenomenon known as RNA interference (RNAi),
regulate a growing number of cellular functions, including many relevant to regen-
erative medicine. Since exogenously introduced, miRNAs or anti-miRNAs (here
commonly referred to as miRNA modulators) can be used to control these events;
their role in regenerative medicine continues to rise [
1
] . MicroRNA modulators can
be used to promote tissue regeneration and engineering in a number of ways. If
injected systemically or locally, miRNA modulators can affect the cells present at
the diseased target site, alleviating the condition either by promoting regeneration
by stimulating the tissue-forming cells [
2
] or by inhibiting further tissue destruction
by modulating the immune system [
3
]. Alternatively, injections of miRNA modula-
tors together with cells can protect and guide the implanted cells to regenerate the
damaged tissue [
4
]. Finally, one can combine cells and miRNA modulators with
implant materials to try and completely create the desired tissue de novo [
5
] , known
as tissue engineering. The number of studies combining miRNA modulators with
cells and implantable materials is still limited; however, information detailing pos-
sible applications and methods for future use can be gained from the prior use of
closely related drugs, especially small interfering RNA (siRNA) [
6
] . An overview
of these strategies can be seen in Fig.
3.1
.
Tissue engineering is showing recent promise. Living blood vessels [
7
] , heart
valves [
8
] , bladders [
9
] , tracheas [
10
] and urethras [
11
] are just some examples of
tissues that have been grown from patient cells and which have subsequently been
implanted successfully, curing diseases. Stem cells are often used when the aim is to
generate new tissue [
12
]. Stem cells are undifferentiated cells with the potential to
generate specialised tissue cells while retaining a pool of undifferentiated cells
through asymmetric cell division. Stem cells can be harvested from embryos (embry-
onic stem cells) in which case they are pluripotent and can be differentiated into all
cell types found in the body. Similar pluripotent stem cells can also be created from
somatic adult cells through a process of dedifferentiation, known as induced pluri-
potent stem cells (IPSC). Different types of stem cells also reside in the adult body,
normally in a non-dividing quiescent state, wherefrom they can be activated to
undergo asymmetric cell division when there is a need for new cells. Cells isolated
from adults are multipotent, meaning that they can be differentiated into a limited
number of cell types. Stem cells can be injected directly as stem cell therapy in
which case they will home to sites of damage and promote repair either by specialis-
ing to replacement cells or by secreting beneficial factors. Stem cells are also com-
monly used for tissue engineering in which case they are usually seeded on a
temporary three-dimensional scaffold; the cells are then induced to differentiate and
create a specific tissue, for example, by modulating their miRNA levels. When the
desired tissue has been generated, preferably replacing the biodegradable scaffold,
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