Stem cells are a promising therapy for stroke and other brain injuries–they can sprout into healthy neurons and may be able to re-establish brain activity in brain-injured patients. While preliminary animal research shows promise, there’s often a common hurdle: adult stem cells have a hard time growing in damaged areas and tend to migrate to healthier regions of the brain.
Scientists are developing nanotube-based delivery devices for stem-cell therapies. Carbon nanotubes (in green) attract growing stem cells (in blue). (Credit: Thomas Webster/Brown University)
That makes sense, says Thomas Webster, associate professor of engineering at Brown University, because healthy neurons emit proteins that attract stem cells away from diseased, inactive areas. What’s needed is an “anchor” to keep stem cells fixed to the damaged areas, where they can then differentiate into working neurons, he says.
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Webster and his collaborators in South Korea found a possible anchor in carbon nanotubes: tiny, highly conductive carbon fibers that not only act as scaffolds, helping stem cells stay rooted to diseased areas, but also seem to play an active role in turning stem cells into neurons.
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Just how this works isn’t clear, but the researchers say their initial results could someday be engineered into a stem cell delivery device for stroke therapy. Webster presented the team’s findings at the American Chemical Society meeting this month in San Francisco.
Prior to this experiment, Webster had been experimenting with the properties of carbon nanotubes as possible neural implant material. Since nanotubes are highly conductive, they’re an ideal template for transmitting electrical signals to neurons. In 2004, Webster was able to stimulate neurons to grow multiple nerve endings along carbon nanotubes. The study attracted the attention of South Korean stroke researchers, who proposed a collaboration: Why not use carbon nanotubes as a template for adult stem cells to grow into neurons? Taking it one step further, the team injected this nano-cocktail directly into the stroke-damaged brain regions of rats.
In order to determine how well the two therapies work together, the team compared the effects of injections of both stem cells and nanotubes with control groups injected with only adult stem cells or carbon nanotubes. After one and three weeks, researchers sacrificed the rats and examined the diseased areas of their brains. In rats who had received only adult stem cells, the cells tended to stray to healthier regions of the brain. But rats given both nanotubes and cells showed new neural growth in stroke-damaged brain regions in as little as a week.
Researchers aren’t sure what makes carbon nanotubes such an effective template for stem cells–or how they help stem cells differentiate. But Webster says a likely answer to both questions is laminin, a glycoprotein in the brain’s extracellular matrix that directs the generation of healthy nerve cells. The surface of carbon nanotubes resembles the elongated shape of laminin, and previous research has shown that nanotubes easily attract and adsorb laminin. Laminin, in turn, has a key amino acid sequence that attracts stem cells, stimulating them to turn into neurons. For these reasons, nanotubes may serve as pro-active delivery devices for stem cells.
“Mechanisms that promote neurogenesis and functional recovery are the keys to success in treating stroke,” says Cindi Morshead, professor of anatomy at the University of Toronto, who studies stem cell therapies for stroke. Morshead sees Webster’s findings as a potentially important step; however, she also cautions that there’s a long way to go before such treatments are proven effective. “It is one thing to make new neurons, but it is entirely a different issue to create cells that are functionally integrated into existing networks that can promote brain repair and behavioral recovery,” she says.
In future trials, Webster’s team will examine behavioral effects over a longer time period, to see if new neurons in diseased areas stay and form long-lasting, functional connections. They will also compare nanotube templates with templates made of silicon and other polymers. Webster suspects that nanotubes will have an advantage over silicon because nanotubes’ outer surfaces resemble natural proteins and tissues in the brain, preventing the body from rejecting them and forming scar tissue.
Todd Pappas, director of the Sensory and Molecular Neuroengineering Department at the University of Texas Medical Branch, who studies signaling neurons and nanotubes, says he thinks nanotubes will eventually be incorporated into prosthetic devices. “But we’re still in the near term, and we’ve got to see what these materials do in the long term,” he says.
