Medicine: Help From The Unborn Fetal-cell

In a widely heralded mercy mission after the nuclear-plant disaster in Chernobyl last spring, Dr. Robert Gale of UCLA and three colleagues flew to the Soviet Union and worked tirelessly to save the radiation victims. Virtually ignored in the reports from the scene was the fact that Soviet physicians and Gale tried a controversial new technique on six of the most severely irradiated Chernobyl workers: fetal-cell surgery. In a desperate attempt to reconstitute the blood-forming tissues of these victims, the doctors transplanted liver cells from human fetuses aborted in the first months of pregnancy.

Those efforts were in vain; all six patients died within a week of the accident. Nonetheless, that Gale used the technique at all reflected the growing confidence of many doctors that fetal-cell surgery could soon become an important medical tool. In the People’s Republic of China, physicians have used fetal-cell implants to treat diabetics. In Sweden, researchers have performed fetal-brain-cell transplants to rid rats of Parkinson’s disease, a progressive and hitherto incurable neural disorder. In the U.S. and elsewhere, fetal-cell experiments with animals have shown promise of treatments for a host of other human disorders, ranging from blood diseases like thalassemia to paralysis caused by spinal-cord damage. Says Neurosurgeon Barth Green of the University of Miami: “This field isn’t growing, it’s exploding.”

But why implant fetal cells into adults? Fetal cells, Gale explains, are “immunologically naive”: during the early stages of pregnancy, they have not yet developed all the antigens, or distinctive surface proteins, that allow the recipient’s immune system to identify and reject them. Another advantage of fetal cells is that they are generally not mature enough to cause graft-vs.-host disease, which can occur when the tissues of a transplant recipient are attacked by implanted adult cells. Also, fetal nerve cells, unlike adult cells, can regenerate and thus have the potential to repair a damaged brain or spinal cord. “These properties,” says Green, “make fetal cells a very exciting glue to tie together injured or diseased areas of the body.”

Of all the uses of fetal-cell surgery, the most successful to date has been the treatment of Type 1 (insulin-dependent) diabetes. This disease, which afflicts about a million Americans, results from the gradual destruction of small islets of insulin-producing cells in the pancreas. Without insulin, the body cannot convert sugars into energy. Even with careful diet and daily doses of insulin, Type 1 diabetes can eventually lead to blindness, kidney failure and strokes.

Past attempts to implant fetal islet cells failed because a small percentage of these cells have antigenic markers that trigger an immune response. “The classic view was that since these antigens were genetically controlled, there was no way to remove them from the cell,” says Kevin Lafferty, an Australian-born immunologist who is director of research at the Barbara Davis Center for Childhood Diabetes in Denver. In 1980, however, Lafferty discovered that culturing islet cells in an oxygen-rich environment for a couple of weeks kills those that bear trigger antigens. Says Calvin Stiller, an immunologist at the University of Western Ontario: “This cultured fetal tissue can be transplanted with impunity.”

Indeed, surgeons at Shanghai People’s Hospital have been treating diabetics with fetal islet cells since 1982. Of 39 patients monitored for more than two years, three no longer need insulin shots and the others have reduced their insulin requirements anywhere from 30% to nearly 100%. In some of these diabetics, the progress of related kidney and eye disease has been either halted or reversed. Results in the U.S. have been less remarkable. Only three of 17 diabetic patients treated so far by Lafferty’s colleague Everett Spees, chief of transplant surgery at AMI St. Luke’s Hospital in Denver, are any less dependent on insulin, and none of them by more than 30%. “We don’t know how long it takes for the fetal tissue to mature,” Spees explains, “nor how much of it we need to treat an adult.”

Swedish researchers at the Karolinska Institute and the University of Lund hope to transplant fetal brain cells into the brains of patients with Parkinson’s disease. Says Dr. Anders Bjorklund: “The cells of an eight-to- twelve-week-old fetus are still developing and can be ‘persuaded’ to take on particular functions.” In this case, the function is producing dopamine, a neurotransmitter that is in short supply in Parkinson’s victims. Bjorklund predicts a trial with humans will begin “within a couple of years.”

Michael Harrison, a pediatric surgeon at the University of California at San Francisco, believes fetal liver tissue may be the key to curing hereditary blood diseases like thalassemia, in which red blood cells carry defective hemoglobin molecules. Reason: fetal liver tissue contains cells that migrate and become bone marrow, the substance that produces blood cells. Harrison has used this tissue to change the blood type of unborn sheep, and is gearing up for a trial in humans. “We’re perfecting our techniques and looking for an appropriate case,” he says. “You don’t want to cut corners on something like this. We need the right circumstances, both biologically and socially.”

Concern about those circumstances extends beyond the medical community. While few object to the use of tissue from fetuses that have aborted spontaneously, the Roman Catholic Church and right-to-life groups draw the line when intentional abortion is involved. But doctors warn that spontaneously aborted fetuses often have genetic defects that make their tissue unacceptable for implantation. As fetal-cell surgery advances, they fear, the need for tissue — whatever the source — will grow. Warns Ethicist Arthur Caplan of the Hastings Center in Hastings-on-Hudson, N.Y.: “The use of fetuses as organ and tissue donors is a ticking time bomb of bioethics.”