HOW’S this for caring? Without being in the same room, building or even the same city as your mother, you can literally patch up her heart. Or your child can patch up yours. It’s an idea that takes getting used to at first, but hear us out: you probably left tiny little bits of you inside your mother. And you got stuff from her, too: her cells take up residence in most of your organs, perhaps even your brain. They live there for years, decades even, meddling with your biology and your health.
Sure, your blood, skin, brain and lungs are made up of your own cells, but not entirely. Most of us are walking, talking patchworks of cells, with emissaries from our mother, children or even our siblings infiltrating every part of our bodies. Welcome to the bizarre world of microchimerism.
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The idea emerged in the 1970s, when were detected in the blood of pregnant women. Until then, we assumed that a mother’s body and her child’s were kept completely separate during pregnancy. Their blood came into close proximity in the placenta – that large, messy bundle of blood vessels connecting mother and child via the umbilical cord – but never actually mixed. Nutrients, oxygen and waste shuttled from one to the other through filters.
We now know that’s only part of the story. “The placenta has been described as having a selective immigration policy,” says Lee Nelson at the University of Washington in Seattle. Along with nutrients and waste, cells also move from one bloodstream to the other. In recent years, we’ve learned that these cells live on for years inside mother and child, as resident aliens. They lodge themselves inside our organs, so that long after birth, a mother’s body is still in some way connected to her child’s. The question is: what are these cells up to? Are they just passengers along for the ride, or do they get actively involved in the life of their host?
Spotting these “microchimeric” cells in the midst of billions of your own is a bit like looking for the proverbial needle in a haystack. To make matters worse, their number waxes and wanes in different organs, and they appear to move around the body. Depending on where you look, someone could appear microchimeric one day but not the next.
Staying power
Still, those who study this phenomenon believe the cells are an inextricable part of us. “If we were able to test lots of samples from multiple points in time and many different sources, we believe we would find microchimerism in most, if not all, individuals,” says Nelson. “I would guess it is ubiquitous.”
What is clear is that the cells get everywhere, have staying power and seem to be associated with both good and poor health. Earlier this year, a study of 26 women who died during pregnancy or within a month of giving birth in every organ tested, including the brain (see “Resident aliens“). Other research has shown that . People who have more of these cells tend to be more prone to certain types of autoimmune disease, but have a lower risk of and , and . The trouble is that many of the earlier studies mainly looked at associations between the number of microchimeric cells in people and the incidence of disease. They stopped short of zooming in on what the cells are really up to.
That is now changing. At Mount Sinai Hospital in New York City, Hina Chaudhry studies a condition called peripartum cardiomyopathy, in which a pregnant woman’s heart becomes weakened and enlarged. “Fifty per cent of women spontaneously recover, and no one knew why,” says Chaudhry. The condition has the highest recovery rate of any form of heart failure.
To see if microchimeric cells from the fetus could be somehow coming to the mother’s rescue, Chaudhry tagged mouse fetal cells with a green fluorescent tracer to track any that crossed into the mother mouse’s bloodstream. Then she induced heart attacks in the pregnant mice. Sure enough, the fetal cells homed in on the damaged heart tissue where they turned into different types of heart cells. “It’s fascinating: they know exactly where to go on their own,” says Chaudhry.
Chaudhry’s most recent studies have shown that a fetus provides a reservoir of embryonic stem cells to the mother. Trophoblast stem cells usually sit on the outer layer of the fetus. During pregnancy, they implant into the wall of the uterus and give rise to the placenta. In her pregnant mice, Chaudhry has found that it is these cells that make their way into the mother’s bloodstream, race to the heart and form brand new beating muscle cells. She believes that the damaged heart tissue may release proteins that act as a beacon to the fetal cells. Her hope is that these studies may one day lead to stem cell therapies that treat different types of heart disease.
“Fetal cells race to the mother’s heart and form brand new muscle cells”
Nelson is particularly interested in what fetal cells are doing in their mothers’ brains. In 2012, she performed autopsies on the brains of 59 deceased women, and found that 63 per cent of them had signs of alien DNA. A 2005 study in mice found fetal cells turning into neurons in their . So could the same thing be happening in humans, helping to form the cells that carry information about your senses, your movement, your thoughts? Nelson and her team are now looking to see if this is the case and are expecting results in the next few months. They are also looking in the opposite direction, to see whether maternal cells reach the brains of their children. “I wouldn’t be surprised if there were maternal cells in the brain,” says Nelson, “and I wouldn’t be surprised if they were an important part of normal development.”
How microchimeric cells interact with our immune system is also a key point of interest. After all, the immune system is there to defend our bodies from invaders, yet microchimeric cells seem impervious to it. That’s promising for things like organ transplants, but how do the cells dip below the immune system’s radar? Nelson’s colleague Hillary Gammill points out that microchimeric cells can turn into a type of immune cell: they literally embed themselves into our body’s defences. Chaudhry is currently looking at the molecules on the surface of microchimeric cells to try to get to the bottom of this.
The health benefits and downsides may not be limited to mother and child. Gammill has looked at how a woman’s cells could give a helping hand to the next generation when she becomes a grandmother. Pre-eclampsia is a complication seen in 6 per cent of pregnancies. In a study of women who developed the condition, Gammill found that none of them carried cells from their own mothers. By contrast nearly a third of the women in the study who didn’t get pre-eclampsia did. Intriguingly, in these women, the number of their mother’s cells in the blood got a boost during the pregnancy’s third trimester, when pre-eclampsia is most common.
Protective hand
The results raise the intriguing possibility of some kind of protective hand being extended to the fetus from their grandmother, says Gammill. Jen Kotler at Harvard University is using the same green fluorescent tags as Chaudhry to trace cells across generations, and see whether cells from grandparents can end up in the brains of their grandchildren.
Why does microchimerism happen at all? Kotler’s colleague David Haig points out that evolutionary pressures may be at play (see “You are multiple, but why?“). “You might expect that [fetal cells] will be enhancing bonding of the mother to the child,” says Haig – thus increasing the child’s chance of survival. “We know there are changes in the brains of mice after pregnancy that are involved with the delivery of maternal care,” says Haig (see “The real baby brain“). “We are raising the possibility that offspring cells could be having a say in the matter as well.”
For Nelson, the weird world of microchimerism turns our understanding of the “biological self” on its head. “To me, the best working paradigm is that we are an ecosystem,” she says, one made up of a patchwork of humans and which can have both positive and negative effects on our health. “Microchimeric cells are present in fairly low numbers, so that will tend to limit their influence,” says Haig. “But small numbers of cells can have big influences. ”
In future, we may be able to invite new helpful humans to join our body’s ecosystem, and encourage less helpful ones to leave. Being human is about to get a whole lot more complicated.
(Image: Paul Tebbott)
Resident aliens
Many organs in our bodies contain cells acquired from other people – but what are they doing?
Brain Cells from fetuses make their way into the mother’s brain. They have been found in several brain regions and may provide protection against Alzheimer’s disease. , but we don’t yet know if the same happens in humans.
Lungs This organ holds more foreign cells than any other, possibly because it contains the first bed of capillaries that blood travels through after leaving the placenta. More blood also passes through the lungs than many other tissues. It has been speculated that microchimeric cells could carry out repairs here.
Breast Alien cells here have been linked to lower rates of . Fetal cells could lengthen lactation and reduce the chances of a mother becoming pregnant again too soon after birth. Think of it as extreme sibling rivalry: the child’s cells are preventing the conception of a new sibling who would sap the mother’s time and energy.
Uterus Fetal cells have been found in the endometrium, the inner lining of the uterus, where they could interfere with the implantation of a new embryo. More sibling rivalry.
Heart Cells transferred from child to mother can repair her damaged heart tissue.
Skin A 2014 study help repair the body after a caesarean section. They are also often found in skin cancers, but further research is needed to discover whether they offer any protection.
You are multiple, but why?
You are more than the sum of your cells. This idea came to prominence in mid-90s, when molecular biologist Richard Jefferson realised that the microbes inside and on us play an integral role in how healthy we are.
Jefferson called the sum of our genes and our microbes’ genes the hologenome. He argued that since our microbes influence health, they also influence our survival and therefore our evolution; we evolved together with them, in a kind of symbiosis.
Microchimerism adds the other human cells within us to the mix. After all, they influence our fitness too (see main story). But why did this evolve in the first place?
Hilary Gammill at the University of Washington in Seattle suggests that microchimerism boosts fitness by linking a mother’s and her child’s ability to fight infections. “It serves both fetal and maternal interests to help mum survive long enough after the birth for the child to become independent,”she says.
Sometimes, the evolutionary interests of mother and child work in opposite directions, says David Haig at Harvard University. In an evolutionary sense, it pays for a mother to have several children – that way, her genes have a greater chance of survival. But from a baby’s point of view, it’s better if mum doesn’t get pregnant again right away. If she does, attention and resources will be divided.
Thanks to microchimerism, says Haig, this rivalry between present and future siblings may be played out in the mother’s body, where fetal cells have been found in both breast and uterus. they could prolong lactation, during which a woman is less fertile. And, he says, fetal cells in the inner lining of the uterus could prevent embryos implanting. “I tend to think of the body as a bit of a collective entity, with different agents having different agendas,” says Haig.
(Image: Patrick Tourneboeuf/Tendance Floue)
A family affair
Swapping cells isn’t just limited to a mother and her child (see main story). Connections may reach much deeper into your family tree.
Take, for example, a woman pregnant with a baby girl, her second child. We know that microchimeric cells can stick around for decades, so it’s easy to imagine cells from her eldest still running around her body. They could get transferred to her new baby. If the eldest was a boy, the daughter now has cells from her brother. These could conceivably be passed on when the daughter has a child of her own – who would therefore have cells from their uncle.
David Haig at Harvard University points to this scenario as a hiccup in studies that assume Y chromosomes found in a woman’s bloodstream must have come from her son. “One thing that I think is crying out to be done is to identify exactly who the cells are from,” he says.
The odds of carrying your sibling’s cells are probably low, says Lee Nelson at the University of Washington, Seattle, but studies suggest it does happen. Rather than just one other human, we could have a whole family album’s worth of cells inside us, all exerting an effect on us (see diagram).
“Another thing to consider,” she says, “is that microchimerism can also occur after a miscarriage.” The same is true for abortions. In both cases, a woman would carry the cells of her unborn child, and any subsequent pregnancies conceivably could pass those cells on to the next generation. It doesn’t stop there. Twins can share cells in the womb, which they then carry out into the world with them.
Finally, consider the fact that more pregnancies begin with twins than end with them. In rare cases, one fetus simply vanishes, absorbed by the mother, the placenta or the other twin. These “vanishing twins” may in fact leave traces of themselves, in their mothers and brothers and sisters.
This article appeared in print under the headline “The others inside you”
