Star cells hold the key
The professor in medical school's Department of Neurosurgery, has, he says, found "the right cells to repair the nervous system" and the right drug to help make that happen. The cells are glial precursor-derived astrocytes that—as their name suggests—can be made from stem cell-like cells called glial precursors. Researchers spike these precursors with bone morphogenetic protein—GDA BMP cells for short. GDA BMP cells require such delicate development from stem cells that Davies and his co-researchers have a patent on their production. Meanwhile, a company called Integra Life Sciences is developing a commercial grade of the anti-scarring drug Decorin, which is critical to allow cells to grow across the site of spinal cord injuries.
Astrocytes (also called star cells) are by far the most common cell in the human nervous system. Some experts estimate that astrocytes comprise more than 60 percent of the nervous system. Surprisingly, very little is known about whether there are different types of astrocytes and what their functions are. It is known however that the embryonic spinal cord has the ability to regenerate without forming a scar, and it is thought that embryonic astrocytes may hold the key to this repair. Glial precursor derived astrocytes with bone morphogenetic protein are therefore not the only astrocytes out there. But Davies and his team think they are the ones found in the embryonic spinal cord that make nerve fibers (called axons) grow most quickly across spine injury sites.
Now, Davies believes that he, his research partner and wife, Jeannette, an assistant professor of neurosurgery, and the rest of his laboratory team have found a way to create the right kind of healing astrocytes. They manipulate the stem cell precursors to a specific point before transplantation. This is critical because stem cell precursors transplanted without manipulation can turn into the wrong kind of astrocyte—one that doesn't heal and causes chronic pain.
"To our knowledge, this is the first time that two distinct sub-types of astrocyte support cells generated from a common stem cell-like precursor cell have been shown to have robustly different effects when transplanted into the injured adult nervous system," Davies explains. "Controlling the development of embryonic stem cells immediately before transplanting them into injured spinal cords is essential, because doctors cannot rely on the injured tissues of the body to create the right types of cells from 'naïve' embryonic stem cells."
Working off two massive computer screens, Davies calls up pictures as exciting as the view of the Rocky Mountains out the glass walls of his ninth floor office. The images show axons tagged a special color growing across the sites of spinal cord injuries in rats. The axons progress along the animal spines and connect with undamaged nerve circuits. On a test course to measure mobility in spine-injured rats, the animals "were walking almost normally after a month," Davies says.
"The previous record for nerve growth was five percent of axons to cross the injury site in one to three months. With the healing astrocytes, what we have are 40 percent of axons growing across in eight days."
The right cells can block pain
There's more. With spinal cord injuries, brain neurons shrink. With GDA BMP cells, the shrinkage in brain neurons drops from 50 percent to just 18 percent, Davies says. Then there is the matter of chronic nerve pain in spinal cord patients. It is called "neuropathic pain" and Davies says it can be so severe it "can even confine normally healthy people to a wheel chair."
"What we would perceive as a light touch, (spinal cord injury patients) perceive as pain," he explains. "What seems warm to us seems burning hot to them."
In animal experiments that didn't use GDA BMP cells, Davies says rats started showing signs of neuropathic pain. Rats that received GDA BMP cells however recovered from spinal injuries and showed no signs of pain. What remains is making sure that scar tissue doesn't impede nerve growth. Davies has found a method of injecting neurons that doesn't cause scar tissue. But he still must deal with scars at injury sites.
"Scars form as a lock-down mechanism to keep bacteria out and protect against infection," Davies says.
Scars also block nerve growth. This led to the second of Davies discoveries: High doses of Decorin injected at injury sites right after an accident help prevent scars from forming. This lets nerve axons grow even faster across spinal injury sites.
"They crossed the barrier in four days (instead of eight)," Davies says.
Combining Decorin with cells like the GDA BMPs will further increase the efficiency of axon regeneration and their ability to make the right connections, Davies adds. For all this to work in a man the size of Christopher Reeve, the nerves would have to grow a couple of feet, Davies admits. Furthermore, the science remains untested in humans. But the potential is such that Davies earned the 2006 Erica Nader Research Award from the American Spinal Injury Association. He was one of a handful of researchers who presented at the 2008 Working 2 Walk conference in Washington, D.C. He lectured on his latest his latest breakthrough—stem cell precursor manipulation to create healing astrocytes—in October 2008 in Beijing at the International Spinal Cord Injury Treatments and Trials Symposium http://chinasci.net/ISCITT/ and at the University of Hong Kong in November 2008. In December 2008 Davies speaks at the Walkoncemore Freedom Ball, http://www.thefreedomball.co.uk/abouttheball.htm, a fund raiser that supports research on spinal cord injuries.
At every venue, Davies emphasizes the need for continued federal spinal cord research funding. "This is not the time to drop the ball in funding medical research," he says. “Hopefully, my field can make good on the promises in years past."
If Stephen Davies leads that field in helping allow spinal cord injury victims the use of their arms and legs, a super scholar will have paid homage to Superman.