Biomedical Engineering Reference
In-Depth Information
culture. As implied from the data and discussion, eventually, the control of cell
behavior including MSC fate decision is achieved by the combinatory functioning
of both elements—biochemical and mechanophysical. With these combined fac-
tors varied, MSCs are affected to exhibit commitment and differentiation markers
specific to a certain lineage. In the long run, MSC differentiation into one lineage
wins over the other lineages under certain extracellular signals. On the other hand,
the degree of commitment and the extent of terminal differentiation are both
substantially altered by the given extracellular cues. Therefore, it is highly rec-
ommended to identify optimal conditions, both biochemical and mechanophysical
and combined, to precisely control the steps of MSC lineage commitment and
differentiation. Specifically for adipogenesis, it is recently highlighted that adipose
cells and their precursor cells, including MSCs, are exposed in vivo to complex
mechanical stimulations and these cells are 'mechanically sensitive and respon-
sive' [
47
]. Reported data illustrate that MSC adipogenesis can be significantly
modulated by external mechanical signals (such as mechanical stretch and micr-
opatterned substrate) and the presence of soluble factors (such as PPARc agonist/
antagonist or BMP4). Further, soluble and mechanical signals often demonstrated
competitive or synergistic control of MSC adipogenesis. Taken all together,
identifying soluble-mechanical conditions to optimally prohibit the adipogenic
commitment and differentiation by MSCs may suggest an unprecedented approach
to treat obesity and related diseases.
Mechanical stretching of adipocytic precursors, MSCs, and preadipocytes, have
produced consistent and concrete results that cyclic stretching of these cells
combined with proper biochemical conditions could inhibit adipogenesis. The
results help support the simple idea that exercise (dynamic stretching of the body)
would decrease fat deposition in the body. This would be seamlessly working if
the macro-stretching of the body induces 'affine' deformation (or homogeneous
deformation as used in solid mechanics) to the cells embedded in the tissues of the
body. However, it is true that in vitro cell stretching studies so far have not really
considered the location of the cells in the body and the precise strain and strain rate
to which cells are exposed in vivo. A more knowledge should thus be obtained to
link in vitro cyclic cell stretching data with its relevance to the in vivo cell
straining situations. MSCs used in many cyclic cell stretch studies for inhibiting
adipogenesis are in majority located within adipose tissues and the bone marrow.
For adipose tissue-derived MSCs, the actual magnitude of strains the cells are
exposed to in vivo is not fully known. For MSCs in the bone marrow, their role in
inducing fat deposition should be identified and whether and how they are exposed
to stretching should be determined. Considering that apparent cyclic stretch effects
to suppress MSC adipogenesis are consistent, the next step would be to determine
underlying molecular mechanisms. If molecular mechanosensor responsible for
the cyclic stretch inhibition of MSC adipogenesis is identified, it may be exploited
as a molecular therapeutic target to deal with obesity. For instance, a pharma-
ceutical agent that induces the activation of such a molecular mechanosensor may
help to enhance the effect of dynamic exercise to inhibit or reduce cellular adi-
pogenesis and obesity. However, it may have to be remembered that varying cell
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