Biomedical Engineering Reference
In-Depth Information
mimic the microenvironment which stem cells are exposed to
in vivo
, we can more efficiently
use stem cells for a variety of applications.
By engineering more relevant ECMs, through physical and molecular interactions,
researchers will be able to directly control stem-cell behavior [55]. This will further enable
our abilities to engineer functional tissue substitutes. Through controlling the chemical,
topographical, and stiffness components of the substrates, we may be able to more accu-
rately control stem-cell fate in synthetic systems. Precise control of stem cells would allow
for further advances within tissue engineering and other biomedical applications [56].
Despite significant advances in these
in vitro
studies, it will ultimately be necessary to dem-
onstrate that stem-cell-based therapeutics are effective
in vivo
. Limitations that exist with
directly injecting or infusing stem cells at the desired site include poor viability and loss of
anchorage. A variety of synthetic polymers with naturally derived components is being inves-
tigated to act as a scaffold for the cells in order to address these problems. The material
architecture is then used to pattern the scaffold in the structure of the desired tissue. One
important factor to consider is that mechanical properties and degradation rates of synthetic
scaffolds are generally co-dependent, which may present challenges when attempting to tune
these properties. Growth factors can be directly bound to the scaffold or encapsulated in
controlled-release systems. Full integration of these therapeutic approaches depends on
mechanical, vascular, and neural integration of the surrounding tissues. Because differentiation
progress, exposure to cytokines and other soluble factors, and inflammation at the site of
delivery impact the state of stem cells after transplantation, the “niche” approach holds
promise [57, 58]. Studies beyond those cited above offer further insight into the state of the art
and the challenges that still exist. Combining the strategies of using chemical, topographical,
and stiffness properties of the ECM to control the behavior and function of stem cells offers
a synergistic and methodical approach to developing effective stem-cell therapies.
References
[1]
McBeath R, D Pirone, C Nelson, K Bhadriraju and C Chen (2004). Cell shape, cytoskeletal
tension, and RhoA regulate stem cell lineage commitment. Developmental Cell 6: 483-495.
[2]
Dalby M, N Gadegaard, R Tare, A Andar, M Riehle, P Herzyk, C Wilkinson and R Oreffo
(2007). The control of human mesenchymal cell differentiation using nanoscale symmetry and
disorder. Nature Materials 6: 997-1003.
[3]
Engler A, S Sen, H Sweeney and D Discher (2006). Matrix elasticity directs stem cell lineage spec-
ification. Cell 126: 677-689.
[4]
Kim D-H, H Lee, Y Lee, J-M Nam and A Levchenko (2010). Biomimetic nanopatterns as
enabling tools for analysis and control of live cells. Advanced Materials 22: 4551-4566.
[5]
Oh S, K Brammer, Y Li, D Teng, A Engler, S Chien and S Jin (2009). Stem cell fate dictated solely
by altered nanotube dimension. Proceedings of the National Academy of Sciences of the USA
106: 2130-2135.
[6]
Nur-E-Kamal A, I Ahmed, J Kamal, M Schindler and S Meiners (2006). Three-dimensional
nanofibrillar surfaces promote self-renewal in mouse embryonic stem cells. Stem Cells 24:
426-433.
[7]
Kshitiz, D-H Kim, D Beebe and A Levchenko (2011). Micro- and nanoengineering for stem cell
biology: the promise with a caution. Trends in Biotechnology 29: 399-408.
[8]
Kim D-H, E Lipke, P Kim, R Cheong, S Thompson, M Delannoy, K-Y Suh, L Tung and
A Levchenko (2010). Nanoscale cues regulate the structure and function of macroscopic cardiac
tissue constructs. Proceedings of the National Academy of Sciences of the USA 107: 565-570.
[9]
Abrams G, S Goodman, P Nealey, M Franco and C Murphy (2000). Nanoscale topography of
the basement membrane underlying the corneal epithelium of the rhesus macaque. Cell and
Tissue Research 299: 39-46.
