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Gabriel A. Silva answers a
few questions about this month's fast breaking paper in the field of
Neuroscience & Behavior.
From
•>>February 2005
-
[late entry]
Field:
Neuroscience & Behavior
Article Title: Selective differentiation of neural progenitor cells by
high-epitope density nanofibers
Authors: Silva,
GA;Czeisler, C;Niece, KL;Beniash,
E;Harrington, DA;Kessler, JA;Stupp, SI
Journal: SCIENCE
Volume: 303
Page: 1352-1355
Year: FEB 27 2004
* Northwestern Univ, Inst Bioengn & Nanosci Adv Med, Chicago, IL 60611 USA.
* Northwestern Univ, Inst Bioengn & Nanosci Adv Med, Chicago, IL 60611 USA.
* Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA.
* Northwestern Univ, Dept Mat Sci & Engn, Chicago, IL 60611 USA.
* Northwestern Univ, Dept Chem, Chicago, IL 60611 USA.
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Why
do you think your paper is highly cited?
Our paper described the next level of neural tissue
engineering, based on the development of our nanomaterials and
their application,
and combined it with stem cell neurobiology, two very
significant areas that may potentially contribute to the
development of novel strategies towards treating neurological
disorders. The potential of bionanotechnology applications to
both basic and clinical neuroscience stems from the potential of
designing and developing nanomaterials and devices that interact
with neurons and other nervous system cells at the fundamental
building block level of these cells: The molecular and protein
scale. This had tremendous potential for the development of new
technologies that may offer new approaches and treatments to
neurological disorders that simply do not exist yet.
Does
it describe a new discovery or a new methodology that's useful to
others?
It describes a new material and the application of that
material to nervous system stem cells that can be potentially
further developed and used by others for targeted clinical
applications, in addition to the already ongoing work. The
potential of bionanotechnology applications to treat central
nervous system disorders and towards the study of neuroscience
is widely appreciated, but meaningful emerging applications
are still rather limited. The work described in our paper
offers an example of the potential of combining
bionanotechnology approaches to the nervous system and nervous
system cells.
Could
you summarize the significance of your paper in layman's terms?
 |
| “Macroglial
Muller cells derived from the rat neural retina
labeled for glial fibrillary acidic protein (GFAP),
a specific intracellular cytoskeletal protein
associated with macroglial cells. A.
Muller cells labeled with anti-GFAP
antibody conjugated quantum dots. B.
Muller cells labeled with anti-GFAP antibodies
by classical immunocytochemistry (red).
The blue label is a non-specific dapi
stain. We are exploring approaches that
will allow us to use the superior optical
properties of quantum dot nanocrystals to study
the levels and distribution of GFAP at higher
resolutions compared with standard molecular
approaches following CNS pathological events.
(The r-MC1 Muller cell line was originally
kindly provided to us by Dr. Vijay Sarthy,
Northwestern
University
,
Chicago
,
Illinois
,
USA
. 605 nm quantum dots were kindly provided
by Quantum Dot Corporation,
Hayworth
,
California
,
USA
.)” |
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The work summarized in our Science paper describes the
self-assembly (i.e., self-organization) of a dense network of
nanofibers (e.g., fibers that are a few nanometers in diameter
but many microns in length) that form from molecules that
normally float in water as individual molecules. But when these
molecules come in contact with the right physiological trigger,
in this case physiological concentrations of cations, positively
charged ions that are ubiquitous in physiological and biological
fluids, these peptide amphiphile molecules self-assemble to form
the nanofiber network. If we use cell culture solutions that
contain a suspension of neural progenitor stem cells as the
trigger, the cells become encapsulated in the interior of the
nanofiber network, which trap the water molecules and forms to
the eye a weak gel (e.g., like a weak Jello). The surface of
these nanofibers are designed to express a molecule that we know
induces the preferential differentiation of the encapsulated
neural progenitor cells into neurons, offering a potential
mechanism to deliver and actively induce neuronal stem cell
differentiation following things like spinal cord injury,
stroke, or retinal degenerations, by injecting the peptide
amphiphile solution into the site of injury and allowing
self-assembly to occur in the body. This approach was not
possible with previous materials or techniques.
How
did you become involved in this research?
My undergraduate and MSc degrees were in human physiology and
neuroscience, respectively. For my Ph.D. I wanted to do
neuroscience research that was more quantitative and
mathematical, so I did a Ph.D. in bioengineering and
neuroscience looking at light adaptation, both experimentally
and theoretically, in photoreceptor neurons in the retina. For
my postdoc, which is where I did the work described in the Science
paper, I wanted to further expand my research tools and explore
an area of applied neuroscience that basically did not exist at
the time: applied nanotechnology to neuroscience and
neuropathology. I was fortunate enough to be able to work with
Professor Samuel I. Stupp, who is Director of the Institute for
Bionanotechnology in Medicine and Professor of Chemistry and
Materials Science and Engineering at Northwestern University in
Chicago. Professor Stupp is a leading expert on
bionanotechnology, in particular to orthopedic and vascular
applications. When I joined his group, Professor Stupp and I
developed a research program that focused on applied
nanotechnologies specifically to neuroscience. And along with
our collaborator Dr. Jack Kessler, Chair and Professor of
Neurology at Northwestern University, and his group, we carried
out the work described in the Science paper.
For an introduction and further reading of
bionanotechnology applications to neuroscience and the nervous
system, please see these several review papers I have written:
- GA Silva (2004) Introduction to nanotechnology and its
applications to medicine. Surgical Neurology
61:216-220.
- GA Silva et. al. (in press—will be published in
the March issue) Nanotechnology approaches for the
regeneration and neuroprotection of the central nervous
system. Surgical Neurology.
- GA Silva (in press- will be published later this year)
Small neuroscience: The nanostructure of the central
nervous system and emerging nanotechnology applications. Current
Nanoscience.

Gabriel A. Silva, M.Sc., Ph.D.
Assistant Professor
Departments of Bioengineering and Ophthalmology
Whitaker Institute for Biomedical Engineering
and Neurosciences Program
University of California, San Diego, CA, USA
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ESI Special Topics,
February 2005
Citing URL - http://www.esi-topics.com/fbp/2005/february05-GabrielASilva.html
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