Helpful Mouse Fetuses Naturally Send Stem Cells to Mom to Fix Her Damaged Heart

By Valerie Ross | November 21, 2011 2:23 pm


Cardiomyocytes damaged by a heart attack

What’s the News: Scientists are devoting countless research hours to treatments based on embryonic stem cells, differentiating these blank-slate cells from embryos into brain cells, light-sensing retinal cells, blood cells, and more to replace damaged or destroyed tissues in the body. Now, a new study in mice shows such that nature has arrived at just such a solution, too: When a pregnant mouse has a heart attack, her fetus donates some of its stem cells to help rebuild the damaged heart tissue.

How the Heck:

  • The researchers started with two lines of mice: normal mice and mice genetically engineered to express green fluorescent protein (GFP), which glows a distinctive green when exposed to blue light, in their cells. They mated normal female mice with GFP-producing male mice. This meant that half the resulting fetuses had the GFP gene, too, making their cells glow, too. Twelve days later—a little less than two-thirds of the way through a normal mouse pregnancy—the researchers gave half the pregnant mice heart attacks.
  • When the scientists examined the female mice’s heart tissue two weeks after the heart attacks, they found lots of glowing green tissue—cells that came from the fetus—in the mom’s heart. Mice who had heart attacks had eight times as many cells from the fetus in their hearts as mice who hadn’t had a heart attack did, meaning the high volume of fetal cells was a response to the heart attack.
  • What’s more, the embryo’s stem cells had differentiated into various types of heart tissue, including cardiomyocytes, the rhythmically contracting muscle cells that produce a heartbeat.

What’s the Context:

The Future Holds: Since fetal stem cells can be readily isolated from the placenta, the researchers point out, they could provide a plentiful source of stem cells for treating heart damage.

Reference: Rina J. Kara et al. “Fetal Cells Traffic to Injured Maternal Myocardium and Undergo Cardiac Differentiation.”Circulation Research, published online November 14, 2011. DOI: 10.1161/​CIRCRESAHA.111.249037

Image courtesy of KGH / Wikimedia Commons

CATEGORIZED UNDER: Health & Medicine, Top Posts
  • http://kforcounter.blogspot.com Cody

    Wow.

  • NightThinker

    “meaning the high volume of fetal cells was a response”

    Or the interchange of cells is a natural phenomena are some particular level of concentration and that the concentration was simply an aspect of the need for the mother’s heart to make use of stem cells. Is there a corresponding amount of available stem cells from the mother in the mother’s system that migrate to the heart for use there? This may be harder to identify as the mother’s stem cells would tend to look like her in situ heart cells as they are, in fact, her own. Has it been ruled out that stem cell migration is not a natural part of the diffusion of resources in a body that supports the repair of damage where ever it occurs? The way I was reading the above article seemed to imply that the fetus responded to the needs of the mother engendered by the heart attack, yet it could be a homeostatic process that is ongoing. It did not mention the concentration of fetal stem cells in the mother’s system overall pre and post induced heart attack.

  • Ryan

    NightThinker,
    I see what you’re saying, but I read it differently.

    “Mice who had heart attacks had eight times as many cells from the fetus in their hearts as mice who hadn’t had a heart attack did, meaning the high volume of fetal cells was a response to the heart attack.”

    So to me that says the fetus is always sharing stem cells with the parent, however in the time of need, they were flooded to the parent in that particular area, even particular cell type (cardiomyocites).

  • sam

    NightThinker,
    you make a fair point. however, the fact that the mother, who initially did not have any genetically engineered GFP’s is the basis for researcher’s entire argument. “1. When the scientists examined the female mice’s heart tissue two weeks after the heart attacks, they found lots of glowing green tissue—cells that came from the fetus 2.It may also explain another curious clinical observation: The hearts of two women who suffered from severe heart weakness were later found to contain cells derived from the cells of a male fetus years after they gave birth to their sons.” The entire point of the article notes that female MI victims, who aren’t pregnant, seem to have a harder time recovering. Pre-analysis and clinical deduction aside, you can’t argue w/ the statistics also related to human observations in pregnant women w/ end-organ damage vs non-pregnant women w/ the same damage…

  • Al

    Apparently when a woman with multiple sclerosis becomes pregnant her condition halts until after birth, at which point it can accelerate to beyond it would be if she was not pregnant at all. I wonder this could possibly be related in any regard.

  • http://charles-harvey.co.uk/ Charlie

    Why aren’t the foetus’ cells rejected by the mother’s immune system?

  • ajfkld

    NightThinker, it says in the article that “Mice who had heart attacks had eight times as many cells from the fetus in their hearts as mice who hadn’t had a heart attack did.”
    So we assume that yes, mice mothers that did not have heart attacks had at least a small amount of GFP cells (or stem cells) in their bodies. I do not believe it could be a homeostatic process because if it was, the cells used to repair the damaged cardiomyocytes would not be glowing (i.e. they would not be from the fetus).

  • Daylight

    The part you seem to have missed, NightThinker, is that “Mice who had heart attacks had eight times as many cells from the fetus in their hearts as mice who hadn’t had a heart attack”. The cells from the fetus were, as the experiment describes, easy to identify due to the gene mutation.

    “Is there a corresponding amount of available stem cells from the mother in the mother’s system that migrate to the heart for use there?”

    This statement is largely irrelevant. The point is that the Fetal stem cells went to the mother’s heart to help it heal. It doesn’t matter if the mother’s body helped itself too, it matters that the fetus helped.

    “Or the interchange of cells is a natural phenomena are some particular level of concentration and that the concentration was simply an aspect of the need for the mother’s heart to make use of stem cells.”

    This is the definition of a “response”. The body/fetus responded in a way to change the concentration and use of the stem cells to heal the mother’s heart.

  • lolmedicine

    The GFPs were seen in the mice hearts after the heart attacks were induced. The GFPs having come from the fetal stem cells, having not been seen prior to the heart attack probably led to the inference that “the high volume of fetal cells was a response.” Additionally these GFPs were not seen in the hearts of mice who did not have heart attacks.

    The researchers are suggesting that the stem cell migration is a natural part of the diffusion of resources in the body that supports the repair of damage where ever it occurs. They state this. However, the specific research done here has only focused on heart tissue.

    If this were a homeostatic process, mice with and without heart attacks would not show a difference in the number of GFP tagged fetal stem cells.

  • Ryan

    @NightThinker You are obviously intelligent which is why it baffles me that you totally missed the fact that there was a control population. Read the part where it discussed how pregnant mice who had not been given a heart attack only had one eighth the glowing tissue in their heart.

  • Paradox

    @NightThinker:

    The concentration of cells in the mother’s heart must, by definition, have come from the fetus due to the presence of the fluorescent protein. Recall that the only source of this protein was from the male mouse who fertilized the female, and therefore from the mouse embryo in her womb. There is no question that those cells came from the fetus, and also no question that there were far more of those cells in mothers who suffered a heart attack.

  • MadDoc

    NightThinker – As with all pop-sci articles you have to take their slant with a grain of salt. I think the cool thing to take away here is that fetal stem cells circulate during pregnancy, are able to be incorporated into the mother’s tissues, and can differentiate in an adult into appropriate tissues. Still pretty darn cool since billions are being devoted to figuring out how to do this in a test tube.

  • Sri

    Night: I think you are right. “Mice who had heart attacks had eight times as many cells from the fetus in their hearts as mice who hadn’t had a heart attack did, meaning the high volume of fetal cells was a response to the heart attack.” My interpretation is that just as there is mixing of fetal and maternal blood, fetal stem cells end up implanting all over the maternal body. In the case of a heart attack, the fetal stem cells replicate and grow, perhaps faster than, native cells (or maybe not) – either way, the cells were already present when the injury took place, but exist in higher amounts due to replication AFTER random seeding, most likely.

  • MikeC2827

    Have you read the full text? It goes into a lot more detail about how they did it. The mother did not express the fluorescent protein gene (eGFP) while the fetus did. They knew the stem cells were of fetal origin because of this protein. They found eGFP+ cells that had markers of cardiomyocytes, smooth muscle cells, and endothelial cells. The results suggest the fetal stem cells had differentiated into cardiac cells. I’m still very skeptical, sounds really interesting though.

    Link to the full text pdf: http://circres.ahajournals.org/content/early/2011/11/11/CIRCRESAHA.111.249037.long

  • http://deepseanews.com/ Al

    Does that mean the mother is a chimaera from that point on? I mean, she is now a mosaic of her cells and those of the fetus right?

  • andrew

    i want to know how you give a mouse a heart attack?

  • Wesley

    @Al yes it does.
    Microchimerism is one of my favourite topics! It’s related to a lot of health changes in the pregnant women that are not fully understood yet

  • Sam

    @Andrew,

    By denying them a cookie, of course.

  • Valerie Ross

    @Charlie — Good question. The mom doesn’t reject the fetal cells because she develops an immune tolerance during pregnancy, in which her body doesn’t attack the cells even though their genetic material differs from her own. Without this immune tolerance, her body would attack the embryo and keep it from growing.
    @andrew — I was wondering that, too: Turns out, the researchers ligated, or tied off, one of the main arteries leading to the mouse’s heart; the lack of blood flow to the muscle caused a heart attack.

  • Martin

    “What did you do today honey..?”

    “I gave a mouse a heart attack.”

  • Ryebread

    To those questioning NightThinker’s reasoning, read his/her post more closely. The premise s/he is questioning is not whether fetal stem cells actually increased in concentration in the mother’s heart as a result of the heart attack; clearly they did. The question is whether or not this was a result of some sort of “fetal response” to the heart attack, or if it was a consequence of there possibly being a certain amount of fetal stem cells floating around in the the mother’s bloodstream, which then responded to the heart attack in the same way the mother’s stem cells presumably did, by attaching to the heart and replicating to repair damaged tissue. The only way to be sure would be to know the total concentration of fetal cells in the mother’s entire body before and after the heart attack, as NightThinker pointed out. Perhaps the researchers examined this and the article left it out, or perhaps something known about stem cell behavior would clarify the situation, but the article doesn’t make that clear.

  • Brian Macker

    So it even happens for mothers without the heart attack. So naturally the next test to do is to let those give birth, then after the fetus is gone to give them a heart attack. Now compare that to the mothers who had a heart attack while pregnant. If there is no difference then and only then can you conclude that the fetus gave more stem cells because of the heart attack.

  • knobody

    i think night’s point is that do we have a way of knowing whether or not MORE stem cells are sent to the mother by the fetus as a response to damage, or are there simply the same number circulating, but more “stick” because of the damage? that is, is the fetus really doing something different or is the response entirely in the mother? i’d be interested to know the volume of stem cells that cross the placenta into the mother’s system both pre and post damage.

  • John Boggs

    I totally agree with NightThinker. It saddens me a little bit that the next half dozen replies missed his (somewhat subtle) point, but not only that; more so that they refuted it. I’ll try to clarify the logical issue that NightThinker was pointing out.

    The article claims that the quantity of stem-cells donated to the mother from the fetus is proportional to the mothers need for stem-cells in some way. That is, that the fetus “responds” to the mothers need for stem-cells. The evidence cited, that the mothers given heart attacks had hearts containing 8 times as many fetus derived cells, does not really justify this claim (that is, there is a much more plausible explanation for this same evidence).

    The explanation is as follows. The fetus does not “respond” to the mother’s injury. Instead, there is a constant rate of cell sharing (fetus cell donation to the mother) regardless of the mother’s condition. This results in some concentration, say K, of fetus stem cells circulating in the mother’s body. The fetus cells leave circulation to be incorporated into the mothers organs, and this occurs at a much faster rate for damaged organs. Now, if you wanted to argue that the fetus “responds” to the mother’s need for stem-cells by sharing more, you would have to show that the total number of stem-cells in the mother’s body increased as a result of the heart attack. The result that the number of stem-cells in the heart increased is insufficient, because it could be that the number of stem-cells in the blood decreased (because stem-cells affixing to the heart and differentiating leave the blood), while the number of stem-cells in the heart increased; but that the total number of stem-cells in the mother’s body did not change. In NightThinker’s words: “it could be a homeostatic process that is ongoing.”

    In case it is still unclear what the idea is, I will describe it as an equilibrium system. The fetus, the mother’s circulatory system, and the mother’s heart are the three components of the system. The fetus is equilibrizes with the mothers circulatory system, and the mother’s circulatory system equilibrizes with the mother’s heart. Given enough time (waiting for all components to come to equilibrium), we expect to find that the concentration of stem-cells in each component of the system is unchanging in time. The three components may not be at equal concentrations (the transfer rates per cell/volume in each direction might be different), but we expect them to be static (unchanging in time). Now suppose that the heart becomes a sink for stem-cells. This results in the concentration of stem-cells increasing in the heart and decreasing in the circulatory system. There has been no “change” or “response” in the fetus; the increased stem-cell concentration in the heart is solely explained by principles of equilibrium.

    Sorry for the long post. It just seemed to me like the majority of responders were missing the point.

  • Frankie

    @Valerie: I can see how the mother’s immune tolerance might allow her son’s stem cells to survive in her body during pregnancy, but don’t see the mechanism by which they avoid attack after the mother’s normal levels of immunity return post-partum? Although the short time period after birth in this study might mean her immune system hadn’t yet reached full competence again, this doesn’t explain the human cases that were long after birth. Is there another tolerance mechanism going on here? Or perhaps it’s just a lucky coincidence that the foetus was similar enough to the mother for her not to recognise these cells as non-self?

  • Marko

    What you all are failing to realize about Night’s post is that he is hypothesizing that the stem cells are naturally transfered over and that the reason for the 8x in the heart was not due to the fetus responding and sending them there but moreso the mother’s body taking them from where they naturally spread out in the body and converging them into the heart.

  • wendy

    The only issue that has not been noted is the fact that this research does not show that there was an increase in stem cells donated by the fetus per se. Rather, it makes sense to say that said stem cells were activated (divided; giving birth to progenitor cells) in mothers who had heart attacks, which would mean that they also express the florescent GFP.

  • Wendy2

    @wendy: Since differentiation into various cell types was detected, that would indeed seem to support the notion that fetal stem cell division, not necessarily more donation, is occurring. Then again, it could also be a combination of both phenomena. Would be interesting if quantitation were possible.

  • Anonymous

    This is all propaganda to convince people into believing that it is ok to use fetuses to harvest stem cells.

  • Bob LaVelle

    Did anyone commenting read the entire study in Circulation Research?

  • Henrietta

    I used to have a congenital VSD hole in the heart… That was until I fell pregnant. Now my cardiologist is shocked at its spontanious closure. I always thought it might have had something to do with the birth of my child….

  • Lauren

    This would also suggest some of genetic material from the male is being incorporated into the pregnant female’s system as well would it not? One theory about how animals choose a mate is that the mother and father’s immune systems will create a child with even better immunity. If this is the case could females not be choosing a particular mate (subconsciously obviously) to improve their own immune system as well?

  • MrsRobinson

    Interesting read :) So much we still do not know!

    @29. Anonymous. You are either a bad troll or haven’t done your homework.

  • Carlye

    Wonder if this may be one reason females live longer than males? If females get an infusion of stem cells when they are pregnant, maybe they get little “fixer upper” repairs in areas that may have some damage, resulting in increased longevity? Just a thought…

  • Amelia

    One clarification: To my knowledge, stem cells from that fetal age are not embryonic stem cells at all. A second- or third-trimester fetus capable of donating extra stem cells is long past being an embryo. Like the stem cells in the cord blood of neonates, they’re “adult” stem cells. Or rather, they are not (non-induced) pluripotent cells anymore.

    Attempting to link the benefits of these fetal stem cells specifically to embryonic stem cells and denying their status as adult stem cells is inaccurate at best. Given the controversial status of embryo-destructive research and the non-controversial status of adult stem cell research, this distinction is culturally important in addition to its scientific significance.

  • http://89beats Susan

    One of my students suffered a massive brain injury following a car accident; she was brain dead. The doctors wanted to pull the plug, but the family would not because she was 2 months pregnant. In her sixth month, blips started showing up on the monitors, by 7.5 months she “woke-up” from her coma when she went into labor. She still has many limitations but walks, talks, and finished high school with a standard diploma, married, and is hoping for the day her son’s stored fetal cord blood can be used to finish healing her.

  • http://www.amu.edu.in Naheed Banu

    What I fee,l it is already written in Quran…..Allah says “I have given you diseases but the cure for them is there within you”….one of them is stem cells. No wonder science will discover many other things. It will be interesting if some other disease is developed and then the transfer of stem cells are studied and their frequency too.

  • http://WWW.ClarkVet.com Anant V Joshi

    When a female receives fetal stem cells during pregnancy, her body starts containing cells with a totally different genetic material than her original Somatic cells. Does this change in the genetic make-up of her somatic cells result in a change in the genetic make-up of her subsequent Germ cells? I think it would! In essence, it is possible that after each pregnancy with a different male, a female’s genetic signature changes because of the incorporation of totally new genes from each new male mating partner. Mind blowing!

  • http://www.sleeperawakes.tumblr.com Ana

    Animal testing is wrong and an insult to real science.
    People aren’t rats, the only thing your learn from studying animals bodies is how the animal’s bodies respond. There is no way to be sure that results from an experiment with mice will translate into something similar in humans until tests are carried out in human subjects, so the animals are an irrelevant part and a waste of time.

  • Teressa

    Hmmm, after reading this article, it sheds some light on what happened to me…I had a heart attack 7 months ago at 33 weeks pregnant, which wasn’t detected until a week later, I was taken to the coronary care unit, 5 days later they did another echocardiogram and to their amazement everything looked normal, I’m wondering whether this was a link…

  • Ash

    Ana, I just wanted to ask you… If you think animal testing is unnecessary, do you expect scientists to straightaway test new cures on humans? Mice are mammals as well. Their bodies may not function 100% like a human body, but at least we can test new medicines/cures on them, so that it may benefit humans later on. If something is cancerous, you will find out in the mice first, instead of killing a person!

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