Cells coax damaged nerves to reconnect

U. ROCHESTER (US) — Researchers have taken a step toward repairing nerves more effectively in patients who have been involved in car accidents or suffered severe injuries.

In a paper published in the journal PLoS One, neurosurgeon Jason Huang and colleagues at the University of Rochester report that a surprising set of cells may hold potential for nerve transplants.

In a study in rats, Huang’s group found that dorsal root ganglion neurons, or DRG cells, help create thick, healthy nerves without provoking unwanted attention from the immune system.

“Our long-term goal is to grow living nerves in the laboratory, then transplant them into patients and cut down the amount of time it takes for those nerves to work,” says neurosurgeon Jason Huang.

Nerve fibers created from DRG neurons. (Credit: University of Rochester)


The finding could pave the way for better treatment for the more than 350,000 patients each year in the United States who have serious injuries to their peripheral nerves. Huang’s laboratory is one of a handful developing new technologies to treat such wounds.

“These are very serious injuries, and patients really suffer, many for a very long time,” says Huang, associate professor and chief of neurosurgery at Highland Hospital, an affiliate of the University of Rochester Medical Center. “There are a variety of options, but none of them is ideal.

“Our long-term goal is to grow living nerves in the laboratory, then transplant them into patients and cut down the amount of time it takes for those nerves to work,” adds Huang.

For a damaged nerve to repair itself, the two disconnected but healthy portions of the nerve must somehow find each other through a maze of tissue and connect together.

This happens naturally for a very small wound—much like our skin grows back over a small cut—but for some nerve injuries, the gap is simply too large, and the nerve won’t grow back without intervention.

For surgeons like Huang, the preferred option is to transplant nerve tissue from elsewhere in the patient’s own body—for instance, a section of a nerve in the leg—into the wounded area. The transplanted nerve serves as scaffolding, a guide of sorts for a new nerve to grow and bridge the gap. Since the tissue comes from the patient, the body accepts the new nerve and doesn’t attack it.

But for many patients, this treatment isn’t an option. They might have severe wounds to other parts of the body, so that extra nerve tissue isn’t available. Alternatives can include a nerve transplant from a cadaver or an animal, but those bring other challenges, such as the lifelong need for powerful immunosuppressant drugs, and are rarely used.

One technology used by Huang and other neurosurgeons is the NeuraGen Nerve Guide, a hollow, absorbable collagen tube through which nerve fibers can grow and find each other. The technology is often used to repair nerve damage over short distances less than half an inch long.

In the PLoS One study, Huang’s team compared several methods to try to bridge a nerve gap of about half an inch in rats. The team transplanted nerve cells from a different type of rat into the wound site and compared results when the NeuraGen technology was used alone or when it was paired with DRG cells or with other cells known as Schwann cells.

After four months, the team found that the tubes equipped with either DRG or Schwann cells helped bring about healthier nerves. In addition, the DRG cells provoked less unwanted attention from the immune system than the Schwann cells, which attracted twice as many macrophages and more of the immune compound interferon gamma.

While both Schwann and DRG cells are known players in nerve regeneration, Schwann cells have been considered more often as potential partners in the nerve transplantation process, even though they pose considerable challenges because of the immune system’s response to them.

“The conventional wisdom has been that Schwann cells play a critical role in the regenerative process,” says Huang, who is a scientist in the Center for Neural Development and Disease. “While we know this is true, we have shown that DRG cells can play an important role also. We think DRG cells could be a rich resource for nerve regeneration.”

In a related line of research, Huang along with colleagues in the laboratory of Douglas H. Smith at the University of Pennsylvania are creating DRG cells by stretching them, which coaxes them to grow about one inch every three weeks.

The idea is to grow nerves several inches long in the laboratory, then transplant them into the patient, instead of waiting months after surgery for the nerve endings to travel that distance within the patient to ultimately hook up.

The first author of the paper is research associate Weimin Liu, Ph.D. Other authors contributed from Hebei Medical University in China and the Fourth Military Medical University in China.

The University of Rochester Medical Center and the National Institute of Neurological Disorders and Stroke funded the project.

More news from the University of Rochester: www.urmc.rochester.edu/news/