Microchimerism: when foetal cells escape

Microchimerism occurs when foetal cells cross the placenta and travel through the mother’s body, sometimes taking up residence in her tissues and even her brain. It might be one way that a foetus tries to help repair some of the damage that pregnancy can do to a woman’s body. At the same time, because these foetal cells can persist in a mother’s body for decades afterwards, it might also explain the surprising surge in autoimmune diseases seen in women who have had children. Eva Higginbotham spoke to Kiarash Khosrotehrani, who is at the University of Queensland...

Kiarash - Microchimerism is something that happens during pregnancy where a very few cells from the baby crossover into the maternal blood, and then go to the maternal circulation and then stick in different tissues.

Eva - And what kind of cells from the foetus are we talking about? Are these, you know, differentiated cells like skin cells, or are they more like stem cells?

Kiarash - There is a bit of randomness in everything that's being transferred. However, as a lot of the cells in the foetus are primitive, there's a large proportion of them that are stem cells and that's what makes them survive long-term and persist for decades in the maternal body.

Eva - That's a really long time! Where are they hanging out?

Kiarash - That's an excellent question. We actually don't know for sure. Where we have found them so far is for example, in the maternal bone marrow. So we can find in the maternal bone marrow, stem cells that have been there for almost four or five decades, or we can find them also in other tissue, where we find them the most, when the mother has some sort of injury, because these foetal STEM cells tend to home towards that injury in the mother and try to fix it, try to repair it, as would the natural STEM cells. So that's where we find the most. And we have been finding these foetal cells in a variety of tissues, in the liver, in the skin, in the thyroid, and so on. But we think that naturally there resides a lot in the bone marrow.

Eva - How do they get by, doing that without being rejected by the mother's body? Because you'd think that the mother's immune system would recognise these cells as non-self and therefore try to get rid of them.

Kiarash - Absolutely. So, we think that at the initial stage, when the transfer happens during pregnancy, these cells benefit from the exact same mechanisms that the mother has in place not to reject the foetus. So during all pregnancy, actually the maternal immune system is sort of dampened, and reduced so that it doesn't react against the foetus, which is something that should be recognised as foreign. So these cells are undergoing the same principles, and then later on, because there are few of them and probably because they're hiding in different places in the maternal body, and don't cause any trouble, they essentially don't generate any danger signal for the maternal immune system. And they're somehow being ignored.

Eva - How do these cells actually cross the placenta? Why are they going across? And also, is this just a normal thing that happens in every pregnancy? Just like a thing that happens, or is it a pathological weird thing?

Kiarash - So this is something that happens in every pregnancy, in really a large set of studies. We can identify these cells in the maternal circulation, if we look hard enough. The reason why they're crossing, we believe are small ruptures of that placental barrier. So between the mother and the foetus, there's always a barrier. And we believe that every now and then, because of movement, because of very small events, this barrier breaks down and a few cells from the foetus can be transferred into the mother, or vice versa, before the barrier is reestablished. In scenarios where this barrier is actually much more disrupted, if the mother, for example, has high blood pressure, if there is any placental abnormality, this transfer happens actually much more frequently and we can find many more foetal cells in the maternal circulation.

Eva - So how many cells are we talking, in a sort of normal pregnancy?

Kiarash - The reason why this was called microchimerism is because of these proportions of one in a million, to one in a billion. So they're quite rare cells. And then when you're talking about what proportion of these are actual stem cells, the rates are even smaller. So, you know, there would be almost one to two cells per litre of maternal blood, that you'd give rise to actually, a whole stem cell population. So they're quite rare.

Eva - What if a mother had multiple children, would that mean that it's likely that she's not just a chimera with one child, but actually with as many kids as she's had pregnancies of?

Kiarash - That's absolutely correct. And there are really strange interactions in terms of how one child influences the microchimerism from the second child, and the third child, there are some groups that have been actually studying that.

Eva - So like sibling cells hanging out in the mother's body, are kind of fighting it out in some way?

Kiarash - Or one immunising the mom against the other, or yeah, there is this type of interaction, exactly.

Eva - Wow. Okay. So it starts early! So can these cells cause any harm in the woman's body?

Kiarash - So there was a whole range of studies, trying to see whether these cells could actually trigger the maternal immune system to react against different tissues, and be maybe responsible for autoimmunity. There's been a number of studies that looked at, for example, the presence of foetal cells in mothers with scleroderma, or systemic sclerosis, which is essentially an autoimmune disease, where the mother's immune system reacts against itself. So these studies have been conducted. There are associations, but they've never been able to show causality, which means that we don't know if the foetal cells are the cause of the autoimmune disease, or they're a consequence of the autoimmune disease homing to the injured tissues to actually try to repair.

Eva - The other pathological thing that I was thinking of is tumours. If you have all these stem cells that are sort of lodging themselves in various locations in the body, do we know if these foetal cells can be responsible for tumours in the mother's body?

Kiarash - As far as it's been studied, we have never found really, malignant tumours being entirely formed of these foetal cells. There have been reports of some benign tissue, especially in the thyroid, where the foetal cells have formed part of it, like benign adenomas, but not really anything that's been malignant and causing metastasis, and so on.