November 07, 2012

Stem cells and nanofibers could enable nerve regrowth and replacement

Eurekalert - Researchers have coaxed cells to grow and myelinate along thin fibers and it has the potential for use in testing treatments for neurological diseases.

They report success in developing polymer nanofiber technologies for understanding how nerves form, why they don't reconnect after injury, and what can be done to prevent or slow damage.

Using polymer nanofibers thinner than human hairs as scaffolds, researchers coaxed a particular type of brain cell to wrap around nanofibers that mimic the shape and size of nerves found in the body.

They've even managed to encourage the process of myelination – the formation of a protective coating that guards larger nerve fibers from damage. They began to see multiple concentric layers of the protective substance called myelin start to form, just as they do in the body.
This shows an oligodendrocyte nerve cell (red/purple) wrapped around a polymer nanofiber (white/clear).

Nature Methods - A culture system to study oligodendrocyte myelination processes using engineered nanofibers.

ABSTRACT - Current methods for studying central nervous system myelination necessitate permissive axonal substrates conducive to myelin wrapping by oligodendrocytes. We have developed a neuron-free culture system in which electron-spun nanofibers of varying sizes substitute for axons as a substrate for oligodendrocyte myelination, thereby allowing manipulation of the biophysical elements of axonal-oligodendroglial interactions. To investigate axonal regulation of myelination, this system effectively uncouples the role of molecular (inductive) cues from that of biophysical properties of the axon. We use this method to uncover the causation and sufficiency of fiber diameter in the initiation of concentric wrapping by rat oligodendrocytes. We also show that oligodendrocyte precursor cells display sensitivity to the biophysical properties of fiber diameter and initiate membrane ensheathment before differentiation. The use of nanofiber scaffolds will enable screening for potential therapeutic agents that promote oligodendrocyte differentiation and myelination and will also provide valuable insight into the processes involved in remyelination.

The research involves oligodendrocytes, which are the supporting actors to neurons -- the "stars" of the central nervous system. Without oligodendrocytes, central nervous system neurons can't effectively transmit the electrical signals that control everything from muscle movement to brain function.

Oligodendrocytes are the type of cells typically affected by multiple sclerosis, and loss of myelin is a hallmark of that debilitating disease.

The researchers have also determined the optimum diameter for the nanofibers to support this process – giving important new clues to answer the question of why some nerves are myelinated and some aren't.

While they haven't yet created fully functioning "nerves in a dish," the researchers believe their work offers a new way to study nerves and test treatment possibilities. Corey, an assistant professor of neurology and biomedical engineering at the U-M Medical School and researcher in the VA Geriatrics Research, Education and Clinical Center, explains that the thin fibers are crucial for the success of the work.

"If it's about the same length and diameter as a neuron, the nerve cells follow it and their shape and location conform to it," he says. "Essentially, these fibers are the same size as a neuron."

The researchers used polystyrene, a common plastic, to make fibers through a technique called electrospinnning. In a recent paper in Materials Science and Engineering C, they discovered new techniques to optimize how fibers made from poly-L-lactide, a biodegradable polymer, can be better aligned to resemble neurons and to guide regenerating nerve cells.

They're also working to determine the factors that make oligodendrocytes attach to the long narrow axons of neurons, and perhaps to start forming myelin sheaths too.

By attaching particular molecules to the nanofibers, Corey and his colleagues hope to learn more about what makes this process work -- and what makes it go awry, as in diseases caused by poor nerve development.

"What we need to do for multiple sclerosis is to encourage nerves to remyelinate," he says. "For nerve damage caused by trauma, on the other hand, we need to encourage regeneration."

8 pages of supplemental information

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