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Fast Breaking Comments

By Gabriel A. Silva

ESI Special Topics, February 2005
Citing URL - http://www.esi-topics.com/fbp/2005/february05-GabrielASilva.html

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.

ST:  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.

ST:  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.

ST:  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 .)”

 

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.

ST:  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.End

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 

ESI Special Topics, February 2005
Citing URL - http://www.esi-topics.com/fbp/2005/february05-GabrielASilva.html

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