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Nano World: Nano for stem-cell research

By CHARLES Q. CHOI   |   June 13, 2005 at 10:37 AM   |   Comments

NEW YORK, June 13 (UPI) -- Cutting-edge nanotechnology is beginning to help advance the equally pioneering field of stem-cell research, with devices that can precisely control stem cells and provide self-assembling biodegradable scaffolds and magnetic tracking systems, experts told UPI's Nano World.

"Nanotechnology might show people once and for all that you really can help regenerate organs with stem-cell biology and help people walk again, help people after heart attacks, help people after stroke," said John Kessler, a neurologist at Northwestern University in Evanston, Ill.

"My own daughter had a spinal-cord injury, and the thought that I could contribute to helping my daughter with this is just overwhelmingly exciting to me," Kessler added.

Stem cells are the primordial cells of the body; every other cell type originates from them. Embryonic stem cells have the power to become any other type of cell, while adult stem cells -- those collected from adults, children or umbilical cords -- only can become certain kinds of cells, such as blood or fat. Scientists hope to create new therapies based on stem-cell implants that repair damaged or lost organs and tissues.

In their natural environment in the body, stem cells transform into other cell types based on chemical triggers they receive from their surroundings.

The exact cues and the placement of those cues for most stem cells are not known, "and our ability to introduce specific chemicals at select locations on a cell is extremely limited," said materials scientist Nick Melosh at Stanford University in Palo Alto, Calif.

Researchers currently must bathe the entire surface of stem cells in various chemicals to search for a response, so Melosh and colleagues are developing a nano lab -- on the scale of billionths of a meter -- to experiment with individual adult stem cells. Each lab essentially consists of a capsule on a silicon chip, around which up to 1,000 nanoreservoirs hold roughly a millionth of a billionth of a milliliter of liquid, comparable to the size of secretions cells use to communicate.

"We are in essence building an artificial cell-interface unit through which we can 'talk' to a stem cell, in much the same way real cells do, through chemical communication," Melosh said. "Nanotechnology is essential for this project. Larger systems just couldn't provide the number of different reservoirs and chemicals within a space small enough to select different areas on a cell."

Future nerve-damage repairs could be accomplished with the aid of stem cells grown in self-assembling three-dimensional biodegradable scaffolds of nanofibers developed by Sam Stupp, a materials scientist working with Kessler at Northwestern.

"When you have nerve fibers try to grow out in the spinal cord, they need something to grow on," Kessler said. "This scaffold gives them physical material to grow across, hang onto."

The fibers, delivered in liquid form, self-assemble into a scaffold within seconds of making contact with the electrically charged ions surrounding cells. An amino acid in the fibers helps promote the growth of neurites -- branches extending from nerves that help the cells communicate. The scaffolds then dissolve as cells grow into place.

Kessler said the preliminary work on repairing spinal-cord damage in mice and rats with neural-progenitor cells is proceeding well. The fibers apparently help prevent the cells from developing into scar tissue around damaged nerves.

"It's important to stress that by no means do we have a treatment for spinal-cord injury yet in humans," he cautioned.

Stupp has established Nanotope, a startup company in Evanston, to bring a product based on the nanoscaffold concept to human trials. Kessler said the scaffolds also could help regenerate "many other organs of the body."

Douglas Kniss, a stem-cell biologist at Ohio State University in Columbus, and colleagues also are developing nanofibrous scaffolds for stem cells.

"The non-cell part of a tissue -- the matrix between the cells -- is important (and) can affect cell function," Kniss explained. "With nanofiber scaffolds, you mimic the nanometer-scale fibers normally found in that matrix. This research could help (address) the critical shortage of transplantable organs."

His team is creating biodegradable scaffolds to nurture fat stem cells. During tumor surgery, doctors often extract fat cells from other parts of the body and transplant them into the tissue from where the tumor was removed.

"You often have scars from donating portions of the body; instead, you can have new fat tissue used in reconstituting those defects," Kniss said.

Kniss and colleagues are developing non-biodegradable three-dimensional scaffolds to hold stem cells for pharmaceutical and biological research.

"You can develop these tissue constructs to test new drugs," he said. "Tissues grow in three dimensions and not two, and three dimensions would be more advantageous for early drug screening."

In the future, magnetic iron-oxide nanoparticles could help physicians ensure they are implanting therapeutic stem cells in the correct location.

"If you inject them in the wrong place, you might inject them into dead tissue, and they would die right away with no nutrients," explained Jeff Bulte, a magnetic-resonance-imaging researcher at The Johns Hopkins University School of Medicine in Baltimore.

In animal tests, researchers have had to remove tissue in order to pinpoint where they implanted stem cells. Using MRI has the potential to track stem cells non-invasively in living animals, but stem cells normally do not easily absorb the magnetic particles doctors inject to enhance MRI scans.

"You need to get a high number of the particles into cells, since the sensitivity of MRI is not very high," Bulte said.

In 2001 Bulte and colleagues reported the first success in MRI tracking of stem cells using magnetic nanoparticles carried into the cells via branch-like nanostructures called dendrimers. Now, he said, the process does not even need dendrimers. Instead, it employs electric pulses that briefly open up pores in stem-cell surfaces, allowing the magnetic nanoparticles to leak in.

"The beauty of it is that it just takes a second. You just mix the nanoparticles with the cells and press a button," he said.

Now Bulte is partnering with two of his Hopkins colleagues --veterinary radiologist Dara Kraitchman and cardiologist Joshua Hare -- to tag magnetically stem cells implanted in heart-attack patients in the hopes of gaining insights into repairing heart damage.

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Charles Choi covers research and technology for UPI Science News. E-mail: sciencemail@upi.com

Topics: John Kessler
© 2005 United Press International, Inc. All Rights Reserved. Any reproduction, republication, redistribution and/or modification of any UPI content is expressly prohibited without UPI's prior written consent.
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