As every little Dutch boy knows, there is more than one way to plug a hole. Scientists trying to help patients with injured spinal cords seem to be taking this lesson to heart. In research centers around the world, they have been perfecting innovative grafting techniques intended to fill voids in damaged spinal cords with new, living cells. Such operations have shown promise in animal studies, allowing paraplegic European rats to stand and quadriplegic American cats to walk. But nobody has had the chance to show definitively that similar transplants could help humans as well--until now.

Image: University of Florida

UNIVERSITY OF FLORIDA TEAM described the innovative spinal surgery on July 12. Richard Fessler, who performed the cell transplant, is at left. The surgery builds on work on cats conducted by Paul Reier (fourth from left) and Douglas Anderson (second from right).
Starting at the beginning of this year, researchers in the United States and Sweden have begun to use fetal cell transplants to treat paralyzed individuals suffering from syringomyelia, a rare degenerative disorder that can develop months or years after a spinal cord injury. In this condition, a syrinx, or fluid-filled cavity, forms near a scar in the cord. Left untreated, these cavities can cause excruciating pain and progressive loss of the sensory and motor capabilities.

In the standard approach, the spinal hollows are drained through an implanted tube, but the tubes tend to get blocked, allowing the cysts to swell again and necessitating yet more surgery. The new techniques may promise a far better solution. During the experimental surgery, doctors first drain the syrinx and then inject it with spinal-cord cells taken from human embryos. Their hope is that these injected cells will grow to fill the drained cavity, patching the hole and somehow preventing it from refilling.

Image: University of Florida

SPINAL SURGERY was carried out by Richard Fessler, who injected the embryonic cells into a cavity in the patient's spinal cord.

Preliminary results are encouraging. Researchers at the University of Florida were cautiously optimistic after a July 11 spinal operation, the first of ten such surgeries to be performed there over the next four years. Neurosurgeon Scott P. Falci of the Craig Center for Spinal Cord Injury Research in Denver, Colo., is even more confident that fetal-cell grafts can obliterate the cysts and the threat they pose to neural function. "The answer to all this is it works," says Falci, who, in collaboration with researchers from the Karolinska Institute in Stockholm, Sweden, has performed the transplant surgery on three patients since mid-January. In each case, he says, magnetic resonance imaging has shown that the grafted cells have indeed grown to fill in the cavity and are living stably within the host spinal cord.

Surprisingly, the transplanted cells need not even be nerves or nerve progenitors. In 1994 Falci filled a cyst in the spinal cord of a quadriplegic with tissue taken from the patient's omentum, the fatty membrane that helps support internal organs. As he reported at the annual meeting of the American Spinal Injury Association in 1995, the operation was a success. Almost four year later, Falci states, the patient remains cyst-free.

Both Falci and neuroscientist Paul J. Reier, a member of the University of Florida team, are quick to emphasize that the innovative surgical techniques were developed only to spackle holes in the spinal cord and prevent further damage; these cellular transplants will not cure paralysis. Still, Reier sees a glimmer of hope that transplanted nerve tissue might provide an "inkling" of improvement in spinal cord function. His own laboratory work has shown that embryonic cell and tissue grafts can stimulate the regrowth of damaged axons and help to reconnect the broken circuits of injured spinal cords in rats and cats. Anecdotal evidence from Russian researchers indicates that paralyzed patients who received fetal-cell transplants may have experienced subtle improvements in sensation and strength, but this work is considered inconclusive.

Even if the subjects in the Florida study experience no such additional benefit, Reier believes that the experiment should pave the way for the development of other spinal transplant techniques, currently under investigation in animal models. The July 11 surgery went very smoothly, Reier remarks, a "straight transfer of lab science to a human setting without a blip." Future work might focus on using grafts of nervous-system stem cells, genetically engineered cells or peripheral nervous tissue (taken from another part of the patient's own body). Of course, the overarching goal of such research is to develop treatments for a broad range of spinal cord injuries. While true spinal cord repair will ultimately involve a variety of treatments, Reier thinks, cellular transplants could be an important component.

More than anything, the fetal transplant surgeries mark a dramatic change in atmosphere from the time in the not-so-distant past when, as Reier puts it, "if you said 'spinal cord injury' and 'repair' or 'regeneration' in the same breath you'd be locked up in La La Land."