http://pubs.acs.org/doi/abs/10.1021/acs.accounts.5b00345
Department of Chemistry and
Chemical Biology, Rutgers, The State University
of New Jersey, 610 Taylor
Road, Piscataway, New Jersey 08854, United States
Acc. Chem. Res., Article ASAP
DOI: 10.1021/acs.accounts.5b00345
Publication Date (Web): December 14, 2015
Copyright © 2015 American Chemical Society
Abstract
Conspectus
The
mammalian brain is a phenomenal piece of “organic machinery” that has
fascinated scientists and clinicians for centuries. The intricate
network of tens of billions of neurons dispersed in a mixture of
chemical and biochemical constituents gives rise to thoughts, feelings,
memories, and life as we know it. In turn, subtle imbalances or damage
to this system can cause severe complications in physical, motor,
psychological, and cognitive function. Moreover, the inevitable loss of
nerve tissue caused by degenerative diseases and traumatic injuries is
particularly devastating because of the limited regenerative
capabilities of the central nervous system (i.e., the brain and spinal
cord).
Among current approaches,
stem-cell-based regenerative medicine has shown the greatest promise
toward repairing and regenerating destroyed neural tissue. However,
establishing controlled and reliable methodologies to guide stem cell
differentiation into specialized neural cells of interest (e.g., neurons
and oligodendrocytes) has been a prevailing challenge in the field. In
this Account, we summarize the nanotechnology-based approaches our group
has recently developed to guide stem-cell-based neural regeneration. We
focus on three overarching strategies that were adopted to selectively
control this process.
First,
soluble microenvironmental factors play a critical role in directing the
fate of stem cells. Multiple factors have been developed in the form of
small-molecule drugs, biochemical analogues, and DNA/RNA-based vectors
to direct neural differentiation. However, the delivery of these factors
with high transfection efficiency and minimal cytotoxicity has been
challenging, especially to sensitive cell lines such as stem cells. In
our first approach, we designed nanoparticle-based systems for the
efficient delivery of such soluble factors to control neural
differentiation. Our nanoparticles, comprising either organic or
inorganic elements, were biocompatible and offered multifunctional
capabilities such as imaging and delivery.
Moving
from the soluble microenvironment in which cells are immersed to the
underlying surface, cells can sense and consequently respond to the
physical microenvironment in which they reside. For instance, changes in
cell adhesion, shape, and spreading are key cellular responses to
surface properties of the underlying substrate. In our second approach,
we modulated the surface chemistry of two-dimensional substrates to
control neural stem cell morphology and the resulting differentiation
process. Patterned surfaces consisting of immobilized extracellular
matrix (ECM) proteins and/or nanomaterials were generated and utilized
to guide neuronal differentiation and polarization.
In
our third approach, building on the above-mentioned approaches, we
further tuned the cell–ECM interactions by introducing nanotopographical
features in the form of nanoparticle films or nanofiber scaffolds.
Besides providing a three-dimensional surface topography, our unique
nanoscaffolds were observed to enhance gene delivery, facilitate axonal
alignment, and selectively control differentiation into neural cell
lines of interest. Overall, nanotechnology-based approaches offer the
precise physicochemical control required to generate tools suitable for
applications in neuroscience.
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