In 1992, a group of University of Florida researchers repaired damaged spinal
cords in cats by implanting neurons from cat fetuses. The aim was "to hit a home
run," explains Douglas Anderson, one of the investigators, who is also with the
Veterans Affairs Medical Center in Gainesville. "The cat's not walking. Can you
make it walk?"
In 40 percent of the cases, Anderson and Paul Reier, both neuroscientists at the University of Florida, did hit a homer. In other words, the graft recipients regained some walking ability.
The researcher's goal was to mimic the trauma of auto accidents, which cause most spinal-cord injuries in this country. They used fetal nerve tissue because it is still reproducing and developing, unlike mature central nervous system tissue.
Why work with cats? Because, says Anderson, there is a "huge body of basic neuroscience data on the animal. And since we had already proven the concept with rats, we needed to move to a higher animal before considering human patients."
And although some neuroscientists work with computer models, they are not nearly advanced enough to simulate the recovery of damaged spinal cords, Anderson points out. "We don't have enough information to program the computer" for normal spinal cord functions. "When you get into the spectrum of pathology, there's such a wide range of variables," Reier adds. "Let's just say that if we could program a computer for all those variables, we wouldn't need to do the research."
To make the animal work as much like the experience of a human spinal cord injury patient, the cats receive the same kind of wound care that Christopher Reeve received after his accident.
For a technique that helped overthrow an axiom of neuroscience -- that adult central nervous system tissue cannot grow -- the graft procedure was relatively straightforward: After allowing the wound to "cool down" for several weeks, the scientists extracted cells from the brain stem or spinal cords of fetal cats and injected the donor cells into the feline "patient." ("Probably the best way is to be least invasive," says Anderson, explaining why they no longer routinely use conventional cut-and-sew grafting techniques.)
Then they compared changes in the patient's mobility to that of animals that had not received a graft, and found that 40 percent of the grafted animals improved significantly more than the controls. Timing makes a difference: 75 percent of cats grafted soon after injury improved, versus 25 to 30 percent grafted 15 weeks afterward.
To refine the timing information, a new series of experiments is comparing
grafts performed soon after injury to grafts performed more than 11 weeks later.
There are arguments for both timings, Anderson says, since most patients
spontaneously improve after injury, and it may be best to allow that to occur
before grafting.
Surprisingly, the Florida scientists have learned that the fetal cells are not
necessarily replacing dead neurons, but may be bringing damaged neurons back
into service. Possibly, the new cells may be restoring essential myelin
insulation on the axons, or providing essential growth factors -- chemicals that
stimulate reproduction of specific kinds of cells.
While restoring neurons may seem less dramatic than replacing them outright,
it can be enough to constitute victory, since living, non-functional neurons are
found "in the vast majority of spinal cord injuries," according to Reier. "The
cord is traumatized, but unless the injury is extremely severe, many fibers are
spared."
Another promising fact that has emerged from the work in Florida and elsewhere
is that small improvements -- what Reier calls "little victories" -- in nerve
function can be priceless to patients. "If you can restore bladder or bowel
function, relieve spasticity, restore sex," he says, "those can bring huge
improvements in quality of life."
Although the human spinal cord has an estimated 20-million axons, only a tiny fraction of them are necessary to restore significant functions. Wise Young, a New York University neuroscientist, notes that surgeons sometimes "remove a tumor from the spinal cord that destroyed 90 percent of the axons, and the patient walks out of the hospital."
Since these smaller improvements are more realistic than dramatic "rising up from the wheelchair" recoveries, the Florida group is "retrenching," says Reier, to focus on improvements that can be quickly translated into the clinic. "We know we can do something, and now we want to give it an acid test by making conditions as realistic as possible. We aren't in the business of doing animal experiments," says Reier. "We're eager to move on. This is very applied research, and our main business is to get it to the patient level." "Everybody talks about a cure," Anderson says, "but our philosophy is that there's probably not one thing that will make anyone get up and walk. It will be a combination of things." Reier adds, "Some groups, including ours, are looking at the combined effects of cellular grafts and trophic [growth] factors, as well as gene delivery," in promoting repair and regrowth of spinal cord.
When will the first human undergo fetal cell transplantation be done? "It could be sooner than you think," Reier answers, adding that the institutional review process is well advanced. "We will be in a position to translate this to people in the near future. We could spend many years being conservative neuroscientists, but we'd end up going down a lot of dead ends. Clinical research will teach us how to do the research work better. And it will help us reach the goal of improving human lives faster."