Robert Hood / Fred Hutch
As every new mother knows, having children changes you – your time and life are irrevocably no longer solely your own. Neither, it turns out, are your cells.
In a strange-but-true phenomenon known as “microchimerism,” mom’s and baby’s cells mix during pregnancy. The term chimerism means that a person carries foreign genetic material in addition to his or her own.
Many of these foreign cells set up shop in different organs, persisting in our bodies for decades or maybe even the rest of our lives. Doctors first spotted mother-child cell sharing more than 100 years ago, but scientists have only recently begun to understand the many ways this mixing affects our health.
My body, your cells
When a woman is pregnant, her blood nourishes the baby by means of the placenta, a special organ that both feeds the fetus and protects it from many infections. We now know that the placenta is not a completely closed border, but rather selectively allows various “immigrant” cells to shuttle back and forth between mom and fetus, said Fred Hutchinson Cancer Research Center’s Dr. J. Lee Nelson, one of the pioneering researchers of the myriad effects of mother-child cell sharing.
Many types of cells make it across the placental border, but the fact that some last past pregnancy suggests that some of the transferred cells are likely stem cells -- immature cells whose future is not yet certain. As babies grow and develop, these cells too are maturing in their new homes. A fetal stem cell that makes its way to mom’s heart may become a heart cell, one that traffics to the liver may become a liver cell, and so on. Recently, Nelson and her colleagues found that baby’s cells can even cross the blood-brain barrier to take up lodging in the mother’s brain.
“We like to think of an individual as more of an ecosystem than an isolated being,” Nelson said.
Although the researchers find traces of fetal cells in the blood of only about one-third of healthy women who have had children, the cells may be present at undetectable levels in many more biological mothers, said Dr. Hilary Gammill, a research associate in Nelson’s group. And moms’ cells persist in their offspring’s bodies as well, meaning that every one of us potentially harbors a few foreign cells amongst our own.
Nature’s bone marrow transplant?
Nelson had been interested in the interplay between pregnancy and autoimmune disorders long before she suspected that microchimerism could play a role. Working at Fred Hutch, where bone marrow transplantation was developed as a treatment for certain blood cancers, she became well-versed in transplantation and its many side effects, including graft-vs.-host disease, or GVHD, where donor cells attack a patient’s organs.
In the mid-1990s, when researchers first learned that fetal cells could last well beyond pregnancy even in healthy women, “a light bulb went off” for Nelson because she realized that the autoimmune disorder scleroderma, which primarily afflicts women, looks a lot like GVHD. She wondered, what if baby’s cells were acting like the transplanted cells responsible for GVHD, sparking mom’s disease years later?
“The thought just appeared, putting those together,” she said.
So she began to investigate a potential tie between scleroderma and fetal microchimersm, and showed that women with this disease indeed have higher levels of fetal cells than healthy women.
But pregnancy can also be beneficial for some autoimmune diseases. Women with the autoimmune disorder rheumatoid arthritis enjoy relief from their symptoms during pregnancy, and Nelson’s team found that the more fetal cells that cross over and the greater the genetic diversity between baby and mom, the greater that relief.
Pregnancy and the breast
If fetal cells in mom can trigger GVHD-like symptoms, Nelson and her colleagues wondered whether the cells also exhibit transplants’ ability to fight cancer. Dr. V.K. Gadi, who got his start on Nelson’s team and now runs his own research group in Fred Hutch’s Clinical Research Division, aims to harness the power of fetal cells to fight breast cancer.
Researchers have long known that pregnancy protects against breast cancer, but clearly this protection is not absolute – many mothers still develop the disease. Gadi was the first to show a link between fetal microchimerism and cancer. He found that among women who have had children, those with lower levels of fetal cells in their bloodstream are more likely to develop breast cancer later in life.
The researchers think that fetal cells might be better than our own bodies at recognizing cancer cells as foreign, and those fetal cells would then alert our immune system to destroy rogue cancer cells before they develop into full-blown disease.
“It’s almost like having a different set of eyeglasses to be able to identify a cell that’s premalignant,” Nelson said.
Now, Gadi is planning a research project that would combine the natural power of mother-child cell sharing with the power of transplants to fight cancer. He wants to test whether transplanting cells donated by a patient’s child could prevent relapse in women with breast cancer who are in remission but are at high risk of their cancer coming back.
“We have the normal transplant we do for medical reasons, but nature does this every day,” he said. “It’s sort of the natural version of the transplant.”
Mother and child vs. leukemia
In another new project, Nelson and Gammill are collaborating with Fred Hutch’s Dr. Colleen Delaney to explore whether microchimerism can boost cord blood’s power to save lives from leukemia. Delaney has developed methods to expand the precious blood stem cells present in an umbilical cord after a baby is born and use these cells as an alternative to traditional bone marrow transplants for those blood cancer patients who can’t find a donor match.
Most of the blood in the umbilical cord comes from the baby, but Gammill has found maternal cells in 70 percent of cord blood samples. Nelson and her research team are beginning to examine whether these cells are cancer fighters as well. They’ll follow the small amounts of maternal cells over time in the transplant recipient to learn whether those cells persist and, if so, whether patients who receive more maternal cells fare better against their cancers.
Overall, Nelson said, there are positive and negative effects of mother-child cell sharing in almost every arena of health her group has studied. She and her colleagues believe that evolutionary forces have driven the good parts of microchimerism to outweigh the bad.
“That seems to be the way biology works,” she said.
“Almost all things in nature are double-edged swords,” Gadi said. On the face of it, human reproduction seems like a bum deal for women, where the father is able to pass on his genes with very little detriment to his health, while the mother does all the physical work required in pregnancy.
“In evolution, it’s hard to find arrangements that are so one-sided,” Gadi said, so maybe microchimerism is one subtle benefit to help even out the playing field.
Rachel Tompa is a staff writer at Fred Hutchinson Cancer Research Center. A native Seattleite, she joined Fred Hutch in 2009 as an editor working with infectious disease researchers and has since written about health and science topics ranging from nanotechnology to global health. She has a Ph.D. in molecular biology from the University of California, San Francisco and a certificate in science writing from the University of California, Santa Cruz. Reach her at firstname.lastname@example.org.
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