A Mother and Child Union: Trading Cells

It’s not exactly the sentimental ideal of Mother’s Day.

Though countless sons and daughters will present mothers with cards that promise to keep Mom in their hearts this Sunday, the truth, alas, is far less poetic. More likely, some of Mom is careening around their bloodstreams, while tiny bits of the children may well be stored in Mom’s spleen.

It turns out that the bonds between a mother and her child are not merely psychological or even genetic: During pregnancy, the mother and the fetus literally exchange cells, leaving identifiable bits and pieces of the child inside the mother – and vice versa – for decades after birth.

A scientifically correct Mother’s Day card might read, “Although you think I am far away, I am always with you,” said Dr. Diana Bianchi, chief of genetics for New England Medical Center in Boston and a mother of two. “It’s a catchy idea that your baby remains with you for the rest of your life.”

But scientists are still wrestling with what this cellular exchange program means for health, particularly for the mother, who can receive an enduring infusion of fetal cells even if she miscarries or aborts the pregnancy.

Some researchers believe lingering fetal cells may contribute to autoimmune diseases by interfering with the mother’s immune system years later. In particular, research has focused on scleroderma, an often fatal build-up of scar tissue in the skin and internal organs, which disproportionately affects women and generally occurs well after childbirth.

But fetal cells – like the children they came from – may also have a good side: A pair of upcoming studies in the journal Arthritis and Rheumatism suggest that some of the fetal cells stored in the spleen may serve as a reserve army of stem cells that can rush in and repair mother’s organs.

Bianchi launched this new line of scientific inquiry five years ago with a report that the fetal cells of sons could be detected in the blood of women for decades after their last pregnancies. Researchers had known for a century that some cells from the fetus sneaked past the placenta into maternal blood, but Bianchi’s finding suggested the cells stick around for a long time.

Researchers call these lingering cells microchimerism, evoking the mythic Greek female monster chimera, which had the head of a lion, the body of a goat and the tail of a serpent. The modern version of the legend is Frankenstein, an equally terrifying composite creature. But scientists say they mean no judgment by the term.

“A lot of people find this physical connection [between mother and child] a source of comfort,” said Dr. Lee Nelson, a rheumatologist at the Fred Hutchinson Cancer Research Center in Seattle. “It gives other people the creeps. It’s interesting that our concept of self is not quite so discrete as we might have thought.”

Indeed, there is a remarkable comingling of parent and fetus despite the placenta that divides them. Hong Kong researchers have found that free-floating fetal DNA accounts for about 3 percent of the total DNA circulating through a pregnant woman. The amount doubles in the last trimester of pregnancy, and increases further with problems such as maternal high blood pressure, premature delivery or male fetuses with Down’s syndrome. Also, pregnancy- related skin eruptions are associated with high numbers of fetal cells congregating in the skin, according to French scientists.

Normal childbirth delivers not only a new baby, but also a surge of fetal cells of an unknown number into the mother’s bloodstream.

No one knows about the health effects of the influx of fetal DNA, but it may well be short-lived, since DNA appears to break down in about 15 minutes in the body. Without a constant resupply, most free- floating fetal DNA clears out of the mother’s blood within two hours of delivery.

But Bianchi’s discovery that fetal cells can stay for decades raised more long-term questions. For the first time, the idea that fetal cells may indirectly trigger malfunctions in the mother’s immune system became a serious hypothesis.

“It came as a surprise,” said Carol Artlett, assistant professor at Thomas Jefferson University in Philadelphia. “Everybody knew fetal cells crossed the placenta, but we didn’t know how long they lived. Now it’s really a race to get as much information as possible.”

The same year Bianchi published her landmark paper on the persistance of fetal cells, Nelson published a paper suggesting that autoimmune diseases, such as rheumatoid arthritis, might be caused by invader fetal cells interfering with the mother’s immune system.

All three research groups – Bianchi in Boston, Nelson in Seattle and Artlett working with rheumatologist Sergio Jimenez in Philadelphia – tackled the problem from various angles, focusing at first on scleroderma, a particularly intractable disease that usual strikes women ages 45 to 55.

They immediately began studies investigating the immunological mechanics of cell-to-cell combat, aiming to find clearer evidence of the dastardly fetal cell’s tricks. They first studied women with sons, because it’s easier to find the Y chromosome of male cells, the most obvious difference from female cells at the molecular level. Other techniques have shown that daughter cells behave similarly to son cells.

Nelson found more fetal cells in the blood of women with scleroderma than in healthy women. Likewise, Artlett discovered large quantities of male cells in the skin of women with scleroderma.

The next clue came from a mouse. In retired breeding mice who had produced scores of litters, Philadelphia researcher Paul Christner could induce a scleroderma-like disease by injecting vinyl chloride, a material found in plastic window blinds and implicated in human scleroderma. In the injected mice, the number of fetal cells detected in the blood increased 50-fold. Fetal cells also infiltrated the skin and swelled the spleen.

The research suggested that fetal cells might combine with an environmental harm to cause disease.

“The jury is still out on whether fetal cells are causing scleroderma or other autoimmune diseases, or the disease process is attracting the persistant fetal cells,” Bianchi said.

Fetal cells, however, may have a good side, according to new work from New England Medical Center. Two studies, soon to be published in the journal Arthritis and Rheumatism, suggests that at least some fetal cells sequester themselves strategically in the spleen, ready and willing to rush in and repair mother’s organs, said Kirby Johnson, assistant professor at Tufts University.

In autopsy specimens of five women with sons and with systemic sclerosis (scleroderma that has spread to internal organs), Johnson detected male fetal cells in organs affected by the disease, and in larger numbers in the spleen compared to women who died of other causes. That suggested that the fetal cells may have been dispatched from the spleen as a kind of cellular repair crew.

A companion paper details the sad story of a woman who died from a particularly viscious case of lupus. In autopsy specimens from her small intestines, which eventually disintegrated and led to her death, Johnson found an enormous number of male cells, presumably from her sons. The cells’ presence suggests they may have been fighting the disease that killed the woman.

The potential benefit of microchimerism comes as a relief to Johnson. His mother has a degenerative liver disease and just a couple of years ago he thought his or his brother’s cells might be to blame. His adopted sister was off the hook. These days, his Mother’s Day message has changed from “I’m sorry” to “You brought me life, and now my fetal cells may be able to return the favor.”

—Carol Cruzan Morton

(Originally published in Multiple Sclerosis Discovery Forum)
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