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March 28, 2001 -- Every year about 1,000 American babies are born with sickle cell disease, an inherited condition affecting the blood that will end their lives at the halfway mark. But researchers think that there may be a way to reach into the womb and stop this inherited disease months before a baby draws its first breath.
The concept is radical: Transplant healthy bone marrow cells into a still-forming fetus that is just barely 3 inches long and weighs just an ounce or so. Those healthy cells would "engraft" or grow together with the developing fetus, and by the time the mother approaches term, the transplanted cells would have replaced the abnormal hemoglobin in the red blood cells.
This invasive treatment is now being developed by researchers at several centers worldwide, says Laurence Shields, MD, associate professor of obstetrics and gynecology at the University of Washington in Seattle.
One of the difficulties in attempting the transplants is knowing the right "mix" or basic formula of stem cells. These cells are harvested from the bone marrow of a donor, Shields says. The cells most useful for transplant to a fetus are called CD34+ cells. But along with the CD34+ cells the bone marrow also includes T cells, or so-called helper cells. These cells help regulate the immune system, the body's natural defense network.
A transplant with too many T cells will cause the body to kill off the newly transplanted cells, a condition called graft vs. host disease, Shields says. But including too few T cells in the mix also can result in failure because the transplanted cells will fail to grow.
Medical experts already have worked out this basic formula for stem cell transplants that take place after birth, but continue to struggle to find the right balance for transplants to a developing fetus.
Shields tells WebMD that already more than 50 of these transplants, called in utero stem cell transplants, have been attempted worldwide. "But only a few have been successful," he says.
He says, however, that work in his lab with monkeys may provide the needed information. By trying several different combinations of T cells and CD34+ cells harvested from the bone marrow of the monkey that sired the fetuses, his team was able to come up with a formula that allowed for successful transplant into the monkey fetuses.
He says, too, that the proper concentration of CD34+ cells as well as the right number of T cells proved crucial. Shields presented findings from this study at a recent meeting of the Society of Maternal and Fetal Medicine in Reno, Nev.
While his studies were conducted in monkeys, not humans, Shields says that the findings are very similar to data collected in studies of sheep. With two classes of mammals yielding similar findings, he says, "it is very likely that it will be the same in humans."
Haywood Brown, MD, clinical professor of obstetrics and gynecology at the Indiana University School of Medicine, tells WebMD that Shields' work is "really the first big positive for this field in that he has demonstrated that stem cells transplanted into a fetus can survive." Brown was program director at the meeting in Reno.
But Shields says successful in utero transplants for humans are still probably "about five years away."
Standing between his monkey studies and safe, successful human in utero procedures are several hurdles.
One, of course, is selecting the patients who could benefit. For example, Shields says that of the 50 or so human in utero transplants that have been attempted worldwide, the successful transplants occurred in cases where the fetus did not have sickle cell disease but another inherited blood disorder called thalassemia. Thalassemia has several different variations, but all types of thalassemia impair the production of normal hemoglobin, the protein that carries oxygen through the blood. Shields says that U.S. researchers tend to concentrate on sickle cell disease because it is more prevalent in this country but worldwide the thalassemias are more common.
In addition to having potential use in treating these conditions, known as hemoglobinopathies, the procedure might be useful in treating disorders like glucogen storage disease, which most often attack the liver.
Another factor in treating many cases is the need to perform the procedure very early in pregnancy, "at about 14 weeks," Shields says. That type of early treatment requires an early diagnosis as well. "At 14 weeks, that would mean a biopsy of the placenta," he says. This procedure, done with a needle, is available at most large university medical centers, he says.
Shields sums up the current state-of-the-art procedure, saying, "Now we have the foundation, so now we can look at ways to enhance grafting. This is the starting point."