Biomedical Engineering Reference
In-Depth Information
In other studies, Winer
et al.
found that it was possible to keep human MSCs quiescent by
culturing them on polyacrylamide substrates designed to mimic the properties of bone marrow.
When cultured on 250 Pa gels, coated with a mixture of collagen type I and fibronectin, human
MSCs halted their progression through the cell cycle. However, when transferred to a culture
of adipocyte induction medium or a stiffer substrate with osteogenic induction medium, they
were able to differentiate either adipogenically or osteogenically, respectively [49]. This study
indicates that signals from the elasticity of the ECM in the bone-marrow niche may play a
critical role in the preservation of pluripotency of stem cells. Thus, as suggested by Dellatore
et al.
, culturing stem cells in a biomimetically defined manner could increase the potential to
produce a large enough number of stem cells for therapeutic uses [50]. Ghosh and Ingber also
suggest that micromechanical properties of the ECM can be applied to controlling stem-cell
lineages for regenerative medicine [51].
However, it is important to consider that different tissues within the body may have
overlapping ranges of elasticities, and it may not be possible to differentiate stem cells into
a specific lineage using a specific stiffness alone. Congruently, a unique stem-cell lineage
may not be defined by a single stiffness, but rather by an acceptable range of stiffness that
is engineered to accomplish a specific goal. Taking this into consideration, Watt and Hogan
also suggest that there is a highly complex relationship between stem cells and their niche,
and stem-cell fate is regulated by both intrinsic and extrinsic signals [52]. Thus, it is important
to take elasticity into consideration when considering the relationship between stem cells
and the ECM, both
in vivo
and
in vitro
, although using the synergistic effect of ECM
stiffness and other ECM components may be the most promising approach for control of
stem-cell fate.
Perspective
These studies and a variety of others offer insight into how stem cells interact with the ECM,
and how these interactions can be utilized for a wide array of stem cell applications
(Figure 3.4). On a chemical level, stem cells are able to bind to and interact with growth
factors, either soluble or bound to the ECM. Growth factors have been shown to play a role
in determining stem-cell-differentiation fate although this alone may not be the most efficient
way to control stem-cell differentiation. Nanoscale topography, including grooves, fibers,
pits, and pillars are able to induce differentiation more adequately than commonly used
two-dimensional culture substrates. This indicates that when stem cells encounter different
nanoscale topographies
in vivo
, this may be a trigger to begin differentiation into different
lineages. Extracellular-matrix stiffness has also been shown to play a role in stem-cell fate, but
the overlap of tissue stiffness ranges
in vivo
prevents using stiffness as the solitary way to con-
trol differentiation. Based on the progress made thus far, it is vital to understand how the
components of the ECM, including chemical make-up, topography, and stiffness, affect the
behavior and function of stem cells. This research may provide further insight into how stem-
cell differentiation, migration, and proliferation are regulated
in vivo
and then may be applied
to practical applications in tissue engineering and regenerative medicine.
Future research into the mechanisms with which stem cells interact with the ECM will
allow researchers to better design the stem-cell niche
in vitro
[53]. Successful culture of stem
cells will allow for wider usage for translational research and eventually clinical applications.
Because stem cells are not yet fully understood, their culture
in vitro
is not yet fully opti-
mized. However, it is quickly becoming apparent that researchers need to shift away from
relying on two-dimensional polystyrene culture with growth-factor-laden differentiation
medium to control the fate of stem cells [54]. By engineering culture environments that
