Biology Reference
In-Depth Information
osteogenesis and adipogenesis, one could instead use miR-148b and miR-371,
respectively [
36,
52
], to grow two component tissues such as a spinal disc.
Temporally controlled release of miRNA modulators could be accomplished by
adsorbing one and encapsulating another miRNA modulator or, alternatively, by
encapsulating the nucleic acids in two materials with different degradation rates.
In one study, two growth factors, BMP2 and BMP7, were incorporated into a scaffold
demonstrating the feasibility of the latter method [
89
]. Here BMP2 acts to promote
early stage osteogenesis, while BMP7 accelerates late stage osteogenesis. The differ-
ential release profile was accomplished by encapsulating the proteins into micropar-
ticles made of either fast degrading poly(lactide-co-glycolide) or slow degrading
poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which were subsequently adsorbed
onto chitosan fibre mesh scaffolds. The sequential release system, releasing first
BMP2 and then BMP7, demonstrated superior bone formation over scaffolds
releasing the two growth factors simultaneous or a reversed sequential manner. This
approach illustrates the benefits of temporal control of drug delivery. Similarly, if
one desired to differentiate embryonic stem cells to osteoblasts, one could suggest a
strategy that involves rapid and delayed release of two different miRNA modulators.
For example, anti-miR-290 could be released rapidly to promote mesodermal dif-
ferentiation followed by a delayed release of miR-148b to promote subsequent
osteoblastic differentiation of the mesodermal cells [
28,
36
] .
3.4.3
Secreted MicroRNAs and Regenerative Medicine
Recent findings indicate that miRNAs may play an even greater role than previ-
ously thought. Traditionally, miRNAs have been regarded as endogenous regulators
of the cells wherein they are expressed. However, secreted vesicular bodies (includ-
ing the smaller exosomes [
90
] and the larger microvesicles [
91
] ) have been shown
to carry mRNA and miRNA between cells as a form of nature's own miRNA drug
delivery [
92
]. MicroRNAs may, thus, serve as paracrine messengers. Adipocytes,
for example, are known to coordinate lipid synthesis using secreted vesicular
miRNA [
93
]. The presence of miRNA in all tested body fluids and the fact that it can
be transferred between different cell types indicate that RNA may prove to represent
a whole new level of endocrine signals [
94
]. Little research has been done on the
role secreted miRNAs play in tissue development and repair. However, it is known
that embryonic stem cells secrete miRNA-loaded vesicles capable of cell transfer
[
95
], and MSCs secrete miRNAs that repress differentiation and may play a role in
coordinating stem cell differentiation [
96
] . The fi rst therapeutic applications of
miRNA-carrying vesicles in relation to regenerative medicine have already been
performed. For example, MSC-secreted microvesicles were found to carry miRNA
involved in cell survival, cell differentiation and organ development [
97
] , and intra-
venous injections of such microvesicles could alleviate glycerol and ischemia rep-
erfusion injury-induced acute and chronic kidney damage [
98,
99
] . Furthermore,
miRNA-carrying microvesicles seem to play a major role in angiogenesis and are
Search WWH ::
Custom Search