Biomedical Engineering Reference
In-Depth Information
stretch conditions and regimens may result in different results, for example,
noncyclic stretching of the cells may lead to opposite effect of inducing adipo-
genesis and increasing obesity.
In contrast to cell stretching, there is little study on compression and fluid flow
targeting adipogenesis. Compression of the cells may be involved in reducing
adipogenesis but more in inducing chondrogenesis and osteogenesis. It is well
established that fluid flow has a strong potential of stimulating osteoblastic dif-
ferentiation for both MSCs and bone cells but very few flow study proposed the
inhibitory control of adipogenesis. It is clear that compression and fluid flow give
different forms of mechanical stimulation to the cells compared with cell stretch.
Thus, in depth comparison of mechanical stimulation modes among stretch,
compression, and fluid flow will provide a new insight regarding how to block the
adipogenesis by mechanical stimuli. It is, on the other hand, noteworthy that in
many cases mechanical stimulations observed in vivo occur in the mixed form and
it may be very difficult to assess the individual contribution to the combined
effects. For example, extracellular matrix deformation such as bending produces
tension (stretching) on one side and compression on the other side. Also, tissue
deformation as is defined by tension or compression usually accompanies inter-
stitial fluid flow through the tissue. Therefore, established cell stretch data may
already include the effects from the other form of mechanical stimulations. More
studies should be dedicated to correctly assess individual and combined effects of
various mechanical loading modes in controlling MSC fate decision including
adipogenesis.
It is also apparent that substrates are very important in directing MSC differ-
entiation toward a particular lineage. Creating the right growth environment is
essential if MSCs are to become a certain type of cell. The organization of ECM
proteins, substrate microscale and nanoscale topographies, substrate rigidity, etc.,
all affect the differentiation of MSCs. While many biomaterials studies have
invested efforts on the fabrication of biomaterials that can induce enhanced or
accelerated differentiation of MSCs toward specific lineages (e.g., musculoskeletal
lineages) for tissue engineering purposes, some studies did test the MSC fate
selection by biomaterial cue including adipogenesis. Specifically, micropatterned
ECM proteins in varying size, shape, and organization have demonstrated that
substrate micro and nanopatterning can selectively lead MSCs to commit to
osteogenesis versus adipogenesis. Furthermore, these studies demonstrated the role
of cell tension signaling in this regulation, suggesting the importance of 'static'
mechanical signal from the substrate to ultimately regulate the fate of the MSCs.
While substrate-induced inhibition of MSC adipogenesis may not have a direct
relevance
to
obesity,
this
may
provide
valuable
templates
for
studying
the
molecular mechanisms of MSCs choosing their fate away from adipogenesis.
In conclusion, the main point that can be gathered is that MSC lineage com-
mitment and differentiation are intricate processes and very responsive to changes
in mechanophysical environments. MSC differentiation toward adipogenesis, in
itself and in comparison with osteogenesis, is influenced by mechanical cell
stimulations (stretch, compression, fluid flow) and also by static mechanophysical
Search WWH ::
Custom Search