The Transmigration of Cells, Cellular Memory, Atavism, and all that

[bngenoh]

There is a plethora of information about these topics, so let's collate them.

To begin, Atavism:

Atavism is the tendency to revert to ancestral type. In biology, an atavism is an evolutionary throwback, such as traits reappearing which had disappeared generations before.[2] Atavisms can occur in several ways. One way is when genes for previously existing phenotypical features are preserved in DNA, and these become expressed through a mutation that either knock out the overriding genes for the new traits or make the old traits override the new one. A number of traits can vary as a result of shortening of the fetal development of a trait (neoteny) or by prolongation of the same. In such a case, a shift in the time a trait is allowed to develop before it is fixed can bring forth an ancestral phenotype.[3]

Then cell transmigration:

It has been known for some time that during pregnancy, the placenta enables a two-way trafficking of immune cells between mother and fetus. Some of the exchanged cells are capable of establishing long-lasting cell lines that persist for at least half a century after birth and are immunologically active.

Known as microchimerism, two genetically distinct and separately derived populations of cells are present in the same individual or organ. While it can occur artificially, as with recipients of blood transfusions or bone marrow transplants, it occurs naturally during most pregnancies. For instance, approximately 50-75% of women after giving birth carry fetal immune cells,[1] and about half as many offspring carry maternal immune cells.

The bidirectional fetomaternal trafficking of cells through the placenta is known as "fetal microchimerism" when moving in the fetal -> maternal direction, and "maternal microchimerism" when moving in the maternal -> fetal direction.

While much of the focus on this phenomenon in the past 15 years has been on the possible pathological role that these fetal cells play in contributing to autoimmune diseases in the mother, i.e. the "bad microchimerism" proposed by Nelson JL in 1996,[2] a more positive perspective is beginning to emerge, also known as the "good microchimerism" hypothesis, which "...suggests that persistent fetal cells, instead of inducing a maternal immune response, provide a rejuvenating source of fetal progenitor cells that may have the capacity to participate in maternal tissue repair processes."[3]

Published in the Journal of the American Medical Association in 2004 and titled "Transfer of fetal cells with multilineage potential to maternal tissue," researchers discussed the role that fetal microchimerism may play in responding to maternal injury by developing multilineage capacity in maternal organs. They found evidence that male fetal microchimeric cells had differentiated into maternal epithelial tissues (thyroid, cervix, intestine and gallbladder," indicating their stem-cell like qualities and the possibility that they were contributing to repair and/or regeneration of those injured maternal tissues.[4]

More recently (2012), the journal Circulation Research published a remarkable article titled "Fetal cells traffic to injured maternal myocardium and undergo cardiac differentiation," which investigated the possible explanatory role that fetal microchimerism has in the clinical observation of the high rate of recovery from heart failure in peripartum (occurring during the last month of gestation or the first few months after delivery) cardiomyopathy patients.[5] Their stated objective was to "...determine whether fetal cells can migrate to the maternal heart and differentiate to cardiac cells." The researchers reported the following results:

    "We report that fetal cells selectively home to injured maternal hearts and undergo differentiation into diverse cardiac lineages. Using enhanced green fluorescent protein (eGFP)-tagged fetuses, we demonstrate engraftment of multipotent fetal cells in injury zones of maternal hearts. In vivo, eGFP+ fetal cells form endothelial cells, smooth muscle cells, and cardiomyocytes."

This astounding discovery indicates that fetal stem cells are capable of differentiating into a variety of heart cell types, including "beating cardiomyocytes," and which may heal the mother's physical heart.

It appears that Nature made it possible for the unborn offspring of mammals to save their mother's lives by contributing stem cells which are capable of grafting into tissues, including bone marrow, potentially providing a lifelong source of new healthy cells to replace damaged or dysfunctional ones.

In a future article we will be investigating the role of placental stem cells in explaining the phenomenon of placentaphagy, i.e. the near universal practice of mammals consuming the placenta of their young.

References:
[1] Maternal microchimerism in healthy adults in lymphocytes, monocyte/macrophages and NK cells. Lab Invest. 2006 Nov ;86(11):1185-92. Epub 2006 Sep 11. PMID: 16969370

[2] Nelson JL (1996) Viewpoint. Maternal-fetal immunology and auto-immune disease: is some autoimmune disease auto-alloimmune or allo-autoimmune? Arthritis Rheum 39, 191 - 194.

[3] Fetal cells in maternal tissue following pregnancy: what are the consequences? Hum Reprod Update. 2004 Nov-Dec;10(6):497-502. Epub 2004 Aug 19. PMID: 15319378

[4] Transfer of fetal cells with multilineage potential to maternal tissue. JAMA. 2004 Jul 7 ;292(1):75-80. PMID: 15238593

[5] Fetal cells traffic to injured maternal myocardium and undergo cardiac differentiation. Circ Res. 2012 Jan 6 ;110(1):82-93. Epub 2011 Nov 14. PMID: 22082491

The extent of the transmigration of cells appears to be quite extensive:

YOUR siblings may be closer to you than you thought. Male cells have been found in the umbilical cord blood of baby girls with older brothers, suggesting that the transfer of cells between mother and baby may be more extensive than previously imagined. Indeed, all of us may be walking chimeras.

Previous studies have shown that cells from both mother and fetus can cross the placenta during pregnancy, and survive for decades in the skin, liver, brain and spleen - a phenomenon called fetal microchimerism. There is even evidence that fetal cells may repair damage to the mother's heart during pregnancy.

Other studies have hinted that fetal cells might contribute to autoimmune disease, prompting speculation that fetal cells disperse more widely, possibly passing between siblings and even across generations.

To investigate this, Miranda Dierselhuis of Leiden University Medical Center in the Netherlands and her colleagues analysed umbilical cord blood from 23 newborn girls, 17 of whom had older brothers. In a subset of the samples, they looked for immune cells directed against the male Y chromosome.

Of the 12 girls in the subset with elder brothers, 11 had cord blood containing immune cells against the Y chromosome, suggesting that male cells had somehow crossed the placenta from the mother - presumably entering her body from a male fetus during an earlier pregnancy. In some of the girls, DNA testing revealed direct evidence of male cells in the cord blood (Blood, DOI: 10.1182/blood-2012-02-410571).

"We may be more microchimeric than we imagined," says Dierselhuis, although she cautions that they haven't yet confirmed the source of the male cells.

Curiously, small numbers of male cells were also detected in one of the girls with no older brother, raising the possibility that these cells were from her uncle, passing to her mother during her grandmother's pregnancy. Another possibility is that they originated from an earlier miscarriage of which the mother was unaware.

"It shows just how ubiquitous the exchange of these cells is," says Hilary Gammill of the Fred Hutchinson Cancer Research Center in Seattle. "We used to think of the placenta as a complete barrier."

Last year, Gammill detected cells in the blood of pregnant women that came from their mothers - the grandmother of their fetus. The number of the cells increased as the pregnancies progressed (PLoS One, DOI: 10.1371/journal.pone.0024101).

"We think the mother's cells shape the ability of the developing immune system to learn tolerance," Gammill says. "We wonder if the grandmother's cells are continuing that education process in some way."

The discovery of even wider transfer of cells between siblings and across generations raises the possibility that these cells may influence the course of health or disease in all of us. Several diseases including asthma, type 1 diabetes and certain cancers are less common in younger siblings. "Even in small numbers, some of these cells have stem-like properties, so I think they could influence health," says Gammill.

Meanwhile, an autoimmune disease called scleroderma - which causes hardening of the skin and blood vessels - has also been linked to the presence of fetal cells in the blood, and seems to be more common in younger siblings. "The further you are down the line in birth order, the greater the risk," says Maureen Mayes at the University of Texas in Houston, who has studied the phenomenon (Arthritis Care and Research, DOI: 10.1002/acr.20096). "Multi-fetal microchimerism is one possible explanation," she says.

And Christoph Bucher of the University of Minnesota in Minneapolis reported in 2007 that stem-cell transplants from cord blood between siblings for various types of blood disease appeared to be more successful if the cells came from younger siblings. This hints that a level of tolerance had already developed between donor's and receiver's cells (Blood, DOI: 10.1182/blood-2007-02-076257). Previously it was assumed that cord blood was immunologically naive, but Dierselhuis's study may help to explain this phenomenon.

However, Bucher is cautious about whether the new study will have any immediate clinical impact. "It's a fascinating idea but it's not something that could be exploited clinically at this stage," he says. "More detailed studies are needed to show conclusively that sibling A is in the cord blood of sibling B."

Very tantalizing, "the voices of the ancestors" comes to mind & also "the wisdom of the ages." 

But to give balance, this comment from a netzien applies:

According to the article, male cells (or more specifically, Y chromosome material) were detected, but their source was not identified. Yet the authors jump to a conclusion: these are cells from a previous pregnancy.

But there is another plausible source for the male genetic material: sperm cells. Most married women continue to have sex during pregnancy. So perhaps these sperm cells leave traces of male genetic material, but coming from the father, not a sibling.

[Megan]

Scientific reductionism can completely obscure what is really going on. These quotes suggest to me that there might be a very different way of viewing life processes that would be much more effective. Wish I knew what it was.

[Aragorn]

Thanks, bngenoh. Interesting information!

[bngenoh]

Scientific reductionism can completely obscure what is really going on. These quotes suggest to me that there might be a very different way of viewing life processes that would be much more effective. Wish I knew what it was.

I think systems theory is a step in the right direction, but open systems to be exact, which are far more fascinating, dynamic, and thus rich than closed systems. Open systems make it so that all that can be determined for a given occurrence, is probabilities, that is tendencies, which as I see it is the most fun way to organize, because it makes everything an adventure, no matter the perspective.

From my observations of the phenomenon of life, it is a vast interconnected open system, unified and whole, there are no parts, but there are units.

p.s. You're welcome Aragorn, more to follow.