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Cells of umbilical cord - mom's or son's?

Cells of umbilical cord - mom's or son's?



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Let's say we have a mother giving a birth to a son. In a very clear manner the cells of these two individuals are very different, of course. Yet there is an umbilical cord connecting them. Then there should be a clearly defined "border" somewhere on its way where the mother's cells meet the cells of her son, is that so? How is it even possible?! ;)


Cells of umbilical cord - mom's or son's?

Answer: Son's.

The interface you are looking for is in the placenta. https://en.wikipedia.org/wiki/Placenta

Formally the fetal side of the placenta is called the Chorion frondosum, which develops from the outer cells of blastocyst (trophoblast), and the maternal side of the placenta, Decidua basalis, which develops from the maternal uterine tissue.

How is it even possible?

Immune tolerance in pregnancy or gestational/maternal immune tolerance

The placenta functions as an immunological barrier between the mother and the fetus, creating an immunologically privileged site. For this purpose, it uses several mechanisms

  1. It secretes Neurokinin B containing phosphocholine molecules. This is the same mechanism used by parasitic nematodes to avoid detection by the immune system of their host.

  2. Also, there is the presence of small lymphocytic suppressor cells in the fetus that inhibit maternal cytotoxic T cells by inhibiting the response to interleukin 2.

  3. The placental trophoblast cells do not express the classical MHC class I isotypes HLA-A and HLA-B, unlike most other cells in the body, and this absence is assumed to prevent destruction by maternal cytotoxic T cells, which otherwise would recognize the fetal HLA-A and HLA-B molecules as foreign. On the other hand, they do express the atypical MHC class I isotypes HLA-E and HLA-G, which is assumed to prevent destruction by maternal NK cells, which otherwise destroy cells that do not express any MHC class I. However, trophoblast cells do express the rather typical HLA-C.

  4. It forms a syncytium without any extracellular spaces between cells in order to limit the exchange of migratory immune cells between the developing embryo and the body of the mother (something an epithelium will not do sufficiently, as certain blood cells are specialized to be able to insert themselves between adjacent epithelial cells). The fusion of the cells is apparently caused by viral fusion proteins from endosymbiotic endogenous retrovirus (ERV). An immunoevasive action was the initial normal behavior of the viral protein, in order to avail for the virus to spread to other cells by simply merging them with the infected one. It is believed that the ancestors of modern viviparous mammals evolved after an infection by this virus, enabling the fetus to better resist the immune system of the mother.

Other mechanisms include exposure to immune modulating factors present in seminal fluid from vaginal and oral sex. https://en.wikipedia.org/wiki/Pre-eclampsia#paternal_tolerance


Mothers And Offspring Can Share Cells Throughout Life

Cutting the umbilical cord doesn&rsquot necessarily sever the physical link between mother and child. Many cells pass back and forth between the mother and fetus during pregnancy and can be detected in the tissues and organs of both even decades later. This mixing of cells from two genetically distinct individuals is called microchimerism. The phenomenon is the focus of an increasing number of scientists who wonder what role these cells play in the body.

A potentially significant one, it turns out. Research implicates that maternal and fetal microchimerism plays both adverse and beneficial roles in some autoimmune diseases as well as the prevention of at least one cancer. This double-edged sword in turn has opened new avenues of study of the body&rsquos immune system and the possibility of developing new tests and therapies.

Two of the world&rsquos leading researchers in microchimerism are J. Lee Nelson, M.D., of Fred Hutchinson Cancer Research Center&rsquos Clinical Research Division and V.K. Gadi, M.D., Ph.D., assistant professor of medicine at the University of Washington. Nelson also is a professor of medicine at the University of Washington. Gadi is also a research associate in the Hutchinson Center&rsquos Clinical Research Division.

In 2007, they were the first to report these potentially beneficial effects of microchimerism:

  • In January, Nelson reported the first discovery that cells passed from mother to child during pregnancy can differentiate into functioning islet beta cells that produce insulin in the child. The same study also found maternal DNA in greater amounts in the blood of children and young adults with Type 1 diabetes than their healthy siblings and a control group, implying that the cells may be attempting to repair damaged tissue. There was no evidence that the mother&rsquos cells were attacking the child&rsquos insulin cells and no evidence that the maternal cells were targets of an immune response from the child&rsquos immune system. The findings could lead to new approaches to treating Type 1 diabetes. For example, if maternal microchimerism results in cells that make insulin, a mother&rsquos stem cells might be harvested and used to treat her diabetic child. Such cells would have a genetic edge over donated islet cells from a cadaver that are usually completely genetically mismatched.
  • Last October, a research paper by Gadi and Nelson described findings that suggest fetal cells that persist in a woman&rsquos body long after pregnancy in some cases may reduce the woman&rsquos risk of breast cancer. The scientists examined the blood of 82 women post-pregnancy, 35 of whom had had breast cancer. They looked for male DNA in the blood, presuming it was present due to a prior pregnancy with a male. Fetal microchimerism (FMc) was found significantly more often in healthy women than women with a history of breast cancer, 43 percent versus 14 percent respectively. The scientists concluded that FMc may contribute to the reduction of breast cancer based on the hypothesis that residual fetal cells may provide immune surveillance of malignant cells in the mother. They caution that further studies are needed to confirm the theory.
  • Microchimerism reveals its Jekyll and Hyde personality in the case of autoimmune diseases. In the late 1990s, Nelson&rsquos group was the first to investigate microchimerism in an autoimmune disease:
  • In 1996 Nelson&rsquos lab proposed that fetal microchimerism might in part explain the female predilection to autoimmune disease and they subsequently discovered elevated levels of fetal microchimerism in the blood of women with scleroderma compared to healthy women. Subsequent studies found fetal microchimerism in internal organs and in skin affected by scleroderma.
  • In 1999 Nelson&rsquos group found that maternal microchimerism persists into adult life in individuals who have normal immune systems. They presumed this is due to engraftment with maternal stem cells. Stem cells can become multiple different types of cells. Researchers wondered whether maternal cells can become part of the cells that make up tissues. Scientists found maternal cells in the hearts of infants who died from heart block due to neonatal lupus and identified that most of the maternal cells were cardiac myocytes (heart muscle cells). They theorized that the maternal cells are the target of an immune attack.
  • On the other hand, women with rheumatoid arthritis often have their disease improve or even disappear during pregnancy. A beneficial role of fetal microchimerism was suggested by the research finding that elevated levels of fetal microchimerism significantly correlated with pregnancy-induced amelioration of rheumatoid arthritis.

The Nelson lab has expanded its study of microchimerism into the fields of reproduction, HIV/AIDS and transplantation. For example, scientists are investigating microchimerism in complications of pregnancy, especially preeclampsia, a disorder characterized by high blood pressure in women in their third trimester of pregnancy, and in recurrent pregnancy loss.

Nelson&rsquos group also is investigating maternal microchimerism in patients with HIV and is looking at whether maternal microchimerism levels correlate with whether there is progression or non-progression to AIDS.

Transplantation of stem cells to treat some cancers results in chimerism. Graft-vs.-host disease occurs more often if the cell donor is a woman with prior pregnancies. Tests of female donor cells found they contained male microchimerism, consistent with the interpretation that fetal microchimerism contributes to graft-vs.-host disease. In kidney, pancreas and islet transplantation, Gadi, Nelson and collaborators tested serial serum samples and found that donor-specific microchimerism detection may become a useful non-invasive test for early rejection. This has led to work by several other research groups to therapeutically exploit the principles of naturally-acquired microchimerism in their selection of donors for transplantation.

The discovery that a mother&rsquos cells can turn up in her adult progeny and that fetal cells can occur in women who were once pregnant heralds the emergence of microchimerism as an important new theme in biology.


Details relating to umbilical cord care

There are many doubts that arise regarding caring for the umbilical cord after a baby’s birth. Let’s go over a few:

When is the right moment to cut the cord? Traditionally, medical professionals have cut the umbilical cord immediately after a baby’s birth.

However, the World Health Organization and other researchers suggest waiting between 30–120 seconds before severing the cord.

As a result, the possibility of the baby needing a blood transmission reduces, as does that of suffering an intravenous hemorrhage.

However, if you’re planning to donate umbilical cord blood, the cord will need to be cut immediately.

What does the caring of a newborn’s umbilical cord consist of? The piece of the umbilical cord that remains attached to your child’s belly button will dry up in a matter of days and fall off.

This usually occurs during the first or second day of life. Meanwhile, you should clean the area with isopropyl 70% alcohol and sterile gauze.

According to recent studies, caring for a newborn’s umbilical cord with these substances isn’t absolutely indispensable. You can also just keep the region dry.

However, in areas where the risk of bacteria is high, this cleaning process can help prevent possible infection.

Can I bathe my newborn? Yes, you can, but you must always gently dry the umbilical cord and surrounding area afterwards.

How can I be sure everything is okay? If you think the cord looks strange, or has a strange smell, is bleeding or oozing liquid, talk to you pediatrician.

A very small amount of bleeding is normal (spotting, small stains), but larger amounts should be brought to your doctor’s attention. He or she may prescribe antibiotics to avoid infection.


Baby’s Cells Can Manipulate Mom’s Body for Decades

Mothers around the world say they feel like their children are still a part of them long after they've given birth. As it turns out, that is literally true. During pregnancy, cells from the fetus cross the placenta and enter the mother's body, where they can become part of her tissues.

Related Content

This cellular invasion means that mothers carry unique genetic material from their children’s bodies, creating what biologists call a microchimera, named after the legendary beasts made of different animals. The phenomenon is widespread among mammals, and scientists have proposed a number of theories for how it affects the mother, from better wound healing to higher risk of cancer.

Now a team of biologists argues that to really understand what microchimerism does to moms, we need to figure out why it evolved in the first place.

“What we are hoping to do is not only provide an evolutionary framework for understanding how and why microchimerism came to be, but also to assess how this affects health,” says lead author Amy Boddy, a geneticist at Arizona State University.

Maternal-fetal conflict has its origins with the very first placental mammals millions of years ago. Over evolutionary time, the fetus has evolved to manipulate the mother's physiology and increase the transfer of resources like nutrition and heat to the developing child. The mother's body in turn has evolved countermeasures to prevent excessive resource flow.

Things get even more intriguing when fetal cells cross the placenta and enter the mother's bloodstream. Like stem cells, fetal cells are pluripotent, which means they can grow into many kinds of tissue. Once in the mother's blood, these cells circulate in the body and lodge themselves in tissue. They then use chemical cues from neighboring cells to grow into the same stuff as the surrounding tissue, Boddy says.

Although the mother's immune system typically removes unchanged fetal cells from the blood after pregnancy, the ones that have already integrated with maternal tissues escape detection and can remain in mom's body.

Microchimerism can get especially complex when a mother has multiple pregnancies. The mother's body accumulates cells from each baby—and potentially functions as a reservoir, transferring cells from the older sibling into the younger one and forming more elaborate microchimeras. The presence of fetal cells in the mother’s body could even regulate how soon she can get pregnant again.

“I think one promising area for further research concerns unexplained pregnancy losses, and whether older siblings, as genetic individuals, can play a role in delaying the birth of younger siblings,” says David Haig, an evolutionary biologist at Harvard University.

Given all this complexity, microchimeras have been difficult to study until recently, the authors note in their paper, which will be published in an upcoming issue of BioEssays. The phenomenon was discovered several decades ago, when male DNA was detected in the bloodstream of a woman. But the technologies of the time couldn't get a detailed enough picture of the genetics to tease apart the minute cellular situation.

Now, deep-sequencing technologies allow researchers to identify the origin of DNA in a mother’ tissues more comprehensively by sampling many areas in the genome, including genes implicated in immunity. These genes are unique to an individual and thus can help differentiate a mother’s DNA from that of her children with greater precision.

“If the cell populations can be isolated, then modern techniques should allow the genetic individual of origin to be unambiguously identified,” says Haig.

Still, understanding how the fetal cells are interacting with maternal cells is going to be difficult, says Boddy. Little is understood about the cellular signaling that causes fetal cells to regulate maternal physiology.

“It’s likely a negotiation between the maternal body and the fetal cells, where there is an expectation in the maternal body of a certain level of microchimerism that it needs to function properly,” said Boddy. For example, previous experiments showed that when mouse fetal cells are exposed to lactation hormones in the lab, they take on similar attributes to those of mammary cells, hinting that breast tissue may be one hot spot for microchimerism.

“Normal, healthy lactation may be the consequence of the fetal cells signaling to the mother’s body to make milk,” says co-author Melissa Wilson Sayres, also at Arizona State. But previous work has also suggested that the same features that allow fetal cells to integrate into the mother’s tissues—like evading her immune system—also makes them similar to cancer cells, which could lead to greater cancer vulnerability in the mother.

Based on evolutionary reasoning, the authors predict that fetal cells should be found primarily in the tissues that play a role in transferring resources to the fetus. That includes the breast, where they may impact milk production the thyroid, where they can affect metabolism and heat transfer to the baby and the brain, where they may influence neural circuitry and maternal attachment to the child.

The next steps will be to use modern sequencing tools to go looking for fetal cells in these spots, and then begin studying how the cells are communicating in each region of mom's body.

“What is really interesting and novel about this work is putting the issue of microchimerism and maternal health into an evolutionary framework,” says Julienne Rutherford, a biological anthropologist at the University of Illinois at Chicago.

“If these fetal cells are interacting with maternal physiology, where in the maternal body would we expect the greatest effect on function? That’s been a big question mark. Putting this into an evolutionary context was incredibly clever and novel and very exciting. It’s a beautiful example of theory driving testable predictions."

EDITOR'S NOTE: This story has been updated to clarify the results of the study on mouse fetal cells and mammary tissue.


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Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, Brazil

Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, USA

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, Rua do Matão, n. 106, Cidade Universitária, São Paulo, SP, CEP 05508-090, Brazil. Telephone: 55-11-3091-7966 Fax: 55-11-3091-7966Search for more papers by this author

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, Brazil

Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California, USA

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, São Paulo, Brazil

Human Genome Research Center, Department of Genetic and Evolutive Biology, University of São Paulo, Rua do Matão, n. 106, Cidade Universitária, São Paulo, SP, CEP 05508-090, Brazil. Telephone: 55-11-3091-7966 Fax: 55-11-3091-7966Search for more papers by this author

Abstract

The identification of mesenchymal stem cell (MSC) sources that are easily obtainable is of utmost importance. Several studies have shown that MSCs could be isolated from umbilical cord (UC) units. However, the presence of MSCs in umbilical cord blood (UCB) is controversial. A possible explanation for the low efficiency of MSCs from UCB is the use of different culture conditions by independent studies. Here, we compared the efficiency in obtaining MSCs from unrelated paired UCB and UC samples harvested from the same donors. Samples were processed simultaneously, under the same culture conditions. Although MSCs from blood were obtained from only 1 of the 10 samples, we were able to isolate large amounts of multipotent MSCs from all UC samples, which were able to originate different cell lineages. Since the routine procedure in UC banks has been to store the blood and discard other tissues, such as the cord and/or placenta, we believe our results are of immediate clinical value. Furthermore, the possibility of originating different cell lines from the UC of neonates born with genetic defects may provide new cellular research models for understanding human malformations and genetic disorders, as well as the possibility of testing the effects of different therapeutic drugs.

Disclosure of potential conflicts of interest is found at the end of this article.


Abnormalities related to Umbilical Cord

Several abnormalities are associated with the umbilical cord. The cord can be too long or too short. It may connect inappropriately to the placenta or develop to be knotted or compressed. It can lead to problems during pregnancy or during labour and delivery process. In some cases, cord abnormalities are diagnosed before delivery through an ultrasound. However, they usually are not diagnosed until after delivery when the cord is inspected directly.

&rang Single Umbilical Artery

Around 1% of singleton and 5% of multiple pregnancies, i.e., twins, triplets or more, have an umbilical cord that contains only two blood vessels instead of three, i.e., one artery is missing. T he cause of a single umbilical artery is not known. Babies with single umbilical artery may have a higher risk for birth defects such as heart defects, central nervous system defects, urinary-tract defects as well as chromosomal abnormalities. When the single umbilical artery is diagnosed during a routine ultrasound, certain prenatal tests need to be carried out to rule out birth defects. These tests include a comprehensive ultrasound, amniocentesis and also echocardiography which is a special type of ultrasound to evaluate the fetal heart in some cases. Also, the ultrasound after birth is also recommended.

&rang Umbilical Cord Prolapse

Umbilical cord prolapse arises when the cord slips inside the vagina after the membranes, i.e., a bag of waters has been ruptured, before the baby slopes into the birth canal. This complication can be seen in about 1 in 300 births. The baby can lay pressure on the cord as he passes through the cervix and vagina during labor and delivery. Putting pressure on the cord reduces blood flow from the placenta to the baby, reducing the baby’s oxygen supply. It can result in stillbirth unless the baby is delivered usually by cesarean section. Pressure on the cord must be released by lifting the presenting fetal part away from the cord during the preparation of the woman for the prompt cesarean delivery process. The risk of umbilical cord prolapse increases if,

  • The baby is in a foot-first position.
  • The woman is in the pre-term labour phase the umbilical cord is way too long.
  • There is a high amount of amniotic fluid.
  • The woman is delivering twins through the vagina.

&rang Vasa Previa

Vasa Previa arises when one or more blood vessels from the umbilical cord or placenta bypass the cervix beneath the baby. The blood vessels that are unguarded by the Wharton’s jelly in the cord, sometimes tear away when the cervix dilates or when the membranes rupture. This results in life-threatening bleeding. Even if the blood vessels do not tear apart, the baby can suffer from a lack of oxygen because of pressure on the blood vessels. When vasa previa is diagnosed unpredictably at delivery, more than half the affected babies are stillborn. Although, when vasa previa is diagnosed by ultrasound earlier, fetal deaths can be prevented by cesarean section. Pregnant women with vasa previa may have painless vaginal bleeding in the second or third trimester of pregnancy. A pregnant woman can be at increased risk for vasa previa if.

  • She has the umbilical cord inserts abnormally into the fetal membranes, rather than the center of the placenta
  • She has placenta previa, i.e., a low-lying placenta which covers part or all of the cervix or other placental abnormalities

&rang Nuchal Cord

A nuchal cord is a condition when the umbilical cord is wrapped around the fetus’s neck. Symptoms in the baby after birth from a prior nuchal cord include face duskiness, facial petechia, and also bleeding in the whites of the optic area. Complications comprise meconium, respiratory discomfort, anemia, and stillbirth.

More the number of wraps, the higher is the risk. The diagnosis can be made by the decrease in the baby’s heart rate during delivery. Nuchal cords are examined by running the finger over the baby’s neck once the head has come out.

Ultrasound may examine the condition before the labor. If it is detected during delivery, doctors may try to unwrap the cord or if that is not possible the clamping and cutting of the cord can be carried out. Nuchal cords can arise in about a quarter of deliveries. The cause of a nuchal cord is usually due to an excessive fetal movement.

Other reasons for cords moving around the neck of a fetus or result of loose knots include:

  • The umbilical cord is way too long
  • A poor cord structure
  • Excess of amniotic fluid
  • Having twins, triplets or multiples

&rang Umbilical Cord Knots

In some conditions, babies are born with one or more knots in the umbilical cord. Some knots occur during delivery when a baby with a nuchal cord is taken out through the loop. Others occur during pregnancy when the baby moves around. Knots frequently occur when the umbilical cord is way too long and also during the identical-twin pregnancies when these identical twins have a single amniotic sac, and the babies’ cords can be entangled. When the one knot or more knots can be pulled tight, cutting off the oxygen supply, it can result in miscarriage or stillbirth. A tightening knot can cause the baby to have heart rate abnormalities during labor and delivery.

&rang Umbilical Cord Cyst

Umbilical cord cysts are generally out pockets in the cord. There are two types of cysts, true and false cysts. True cysts are lined with cells and mainly contain miscellanies of early embryonic structures. Whereas the false cysts are formed from local degeneration of Wharton’s jelly. Both types of cysts are sometimes associated with birth defects that include chromosomal abnormalities, kidney defects, and abdominal defects. When a cord cyst is diagnosed during an ultrasound, the doctors may recommend additional tests, such as amniocentesis and a comprehensive ultrasound to rule out birth defects.


Results

Characteristics of cord blood harvests used for the in vitro growth of adherent cells.

Thirty-one cord blood harvests were entered and analysed in this study. As seen in Table I, the median values for the haematological parameters analysed were in close agreement with those reported for UCB collections for banking purposes ( 1 5 ). UCB from donors with a wide range of gestational ages (32–41 weeks) were included to establish whether gestational age correlates with the potential of UCB to develop adherent cells in vitro.

Morphological characteristics of primary cultures of UCB-derived adherent cells.

UCB-derived mononuclear cells were set in culture and the onset of an adherent layer was monitored continuously. By day 15 of culture, 29 out of 31 cord blood harvests had produced an adherent layer, which remained as such even after regular changes of the medium.

From 76% of the cord blood specimens analysed, the evolved adherent layer was formed by a heterogeneous population of cells. Based on the morphology of the most abundant phenotype present (Fig 1A and C), cells in this group of cultures were termed osteoclast-like cells (OLCs). In turn, in 24% of the UCB samples evaluated, the adherent layer contained a homogeneous population of cells showing a fibroblastoid morphology (Fig 1B and D). Cells in this group of cultures were termed mesenchymal-like cells (MLCs).

Photomicrographs showing adherent cells from cultures of UCB. Photomicrographs, taken after 30 d in culture, show osteoclast-like (A, C and E) and mesenchymal-like (B, D and F) cells. (A–D) Unstained cells, as visualized by phase contrast microscopy. (E and F) Cells after staining for TRAP and PAS respectively. Magnification: A and D, 100× B, C, E and F, 200×.

Characteristics of osteoclast-like cells

The morphology of OLCs was heterogeneous. Microscopic examination revealed cells with an elongated or oval/round shape with smooth borders, showing in certain cases cytoplasmic extensions. Usually, the cells were in contact with each other, however the most remarkable feature was the presence of multinucleated cells with nuclei congregated around a central area. After 3 weeks in culture, the multinucleated cells tended to predominate over the elongated and small rounded cells (Fig 1C) and reached a semiconfluent condition after 4 weeks. By subcultivation, these cells gave rise again to multinucleated cells, however their proliferation capacity was limited.

As seen in Table II, more than 90% of OLCs were strongly positive for tartrate-resistant acid phosphatase (Fig 1E), acid phosphatase and α-naphthyl acetate esterase activity, but negative for periodic acid–Schiff, sudan black B, alkaline phosphatase and naphthol AS-D chloroacetate esterase activities. As detected by flow cytometry (Fig 2), although all OLCs expressed the common leucocyte antigen CD45, only a subpopulation expressed the monocyte–macrophage antigen CD14. Together, OLCs expressed the osteoclast-related antigen CD51/CD61 (vitronectin receptor), but did not express the macrophage–polykaryon (CD64)-, the mesenchymal (SH2)- or the endothelial (CD31)-related antigens (Fig 2).

Immunocharacterization of osteoclast-like cells. After 5 weeks in culture, OLCs were detached with EDTA, labelled with monoclonal antibodies and enumerated by flow cytometry. Data show contour plot analysis for CD14/CD45 and histograms for CD51/CD61, CD64, SH2 and CD31 expression. Mean intensity of fluorescence of the respective control antibodies was ≤ 5 (not shown).

Characteristics of mesenchymal-like cells

Primary cultures of MLC mainly consisted of colonies of bipolar fibroblastoid cells (Fig 1D) which, after subcultivation, proliferated with a population-doubling time of 48 h and reached a confluent growth-arrested condition (Fig 3A). In primary cultures, the MLC frequency varied from one harvest to another, however in each UCB sample the average number of MLC colonies (day 15) for 25 × 10 6 UCB-derived mononuclear cells was 7 ± 3.

Proliferation and cell cycle analysis of mesenchymal-like cells. Proliferation studies (A), cell cycle analysis (B) and assessment of quiescent (G0) cells (C) were carried out as indicated in the text. For analysis of quiescent cells, quadrant determinations (not shown) were performed as previously described ( 4 ).

Cell cycle analysis (at log phase of growth) indicated that ≥85% of the cells were in the G0/G1 phases (Fig 3B). Analysis to detect quiescent cells revealed that 5% of all MLCs displayed a pattern of RNA and DNA staining which is distinctive for G0 cells (Fig 3C).

Cytochemical analysis (Table II) revealed that MLCs were strongly positive for α-naphthyl acetate esterase and periodic acid–Schiff (Fig 1F), but were negative for all the other cytochemical markers assessed. The immunophenotype of these cells (Fig 4), as studied by flow cytometry, disclosed the homogeneous expression of the mesenchymal-related antigens SH2, SH3 and SH4. Together, MLCs were positive for an antigen (detected by MAB 1470) which although expressed by endothelial cells was also expressed by mesenchymal cells ( 4 ). MLCs expressed antigens CD13, CD29, CD49e, CD54 and CD90 and α-smooth muscle actin (ASMA), but did not express antigens CD14, CD34, CD45, CD49d and CD106. In addition, MLCs did not express the endothelial-related antigens CD31 and von Willebrand factor.

Immunocharacterization of mesenchymal-like cells. MLCs were detached with EDTA, labelled with monoclonal antibodies and enumerated by flow cytometry. Relative number of cells (counts) is presented vs. fluorescence intensity.

Further characterization studies performed on MLCs revealed a potential to differentiate into osteoblasts and adipocytes. Thus, after switching MLCs from the regular culture medium into an osteogenic medium, cells with an osteoblast-like phenotype evolved, as judged by the expression of alkaline phosphatase (Fig 5A) and by the deposition of a mineralized matrix (Fig 5B). Moreover, when MLCs were exposed to an adipogenic medium, cells differentiated into adipocytes which displayed a perinuclear accumulation of lipid vacuoles, as detected by phase-contrast microscopy or after staining with Oil red O (Fig 5C). The above features were not observed in MLC cultures grown in regular culture medium.

Differentiation potential of mesenchymal-like cells. As described in the MATERIALS and METHODS section, cultures of MLCs were exposed to osteogenic or adipogenic medium. Appearance of osteoblasts was detected (day 7) by either alkaline phosphatase expression (A, thick arrow) or by matrix mineralization (A and B, thin arrows). Adipocytes were detected (day 15) by accumulation of lipid drops, that stained with Oil red O (C, thick arrow). Magnification: A and C, 200× B, 40×. Note that before the addition of the switch medium, cells appeared as shown in Fig 1D.


The swift journey from fetus to mother

It's not surprising that cells can be easily exchanged between mother and fetus, said Amy Boddy, a biologist at the University of California, Santa Barbara. That's because humans have one of the most invasive placenta types among mammals — one that rearranges arteries so that there is direct blood flow between the mother and the fetus.

This cell exchange starts about six weeks into a pregnancy and continues for the duration, Boddy told Live Science.

Studies have found that these fetal cells can essentially travel to anywhere in the body. In a 2015 study, researchers found cells that contained Y chromosomes in the brains, hearts, kidneys, lungs, spleens and livers of 26 women who died within one month after pregnancy (all were carrying male babies).

The fact that they can be found in so many different tissue types indicates that they're probably stem cells, or cells that can differentiate into any type of cell, she said. (Indeed, the fetal cells also carry markers on their surfaces that are typical of stem cells, she added.)

The mother's body kills off most of these circulating fetal cells shortly after pregnancy. But some evade the immune system and can stay for long periods of time in the mother's body — in some cases, even a lifetime, she said.

"If [the cells were] integrated into tissue … they can be around for a lifetime," Boddy said. For example, a 2012 study found Y chromosomes in 63 percent of the brains of 59 women — the oldest of whom was 94. That means these weren't women who just gave birth.


What are the major types of stem cells?

Stem cells are broadly classified as either adult or embryonic. Technically, even stem cells that come from fetal tissue or umbilical cord blood are classified as adult stem cells, and so most researchers prefer the term tissue stem cells for all stem cells other than those from embryos.

Embryonic stem cells (ES cells) are obtained by extracting cells from very early embryos — at the blastocyst (hollow ball) stage — and growing them in laboratory dishes. Human ES cells are generated mainly from blastocysts that are the result of in vitro fertilization for assisted reproduction, but are not needed for implantation into the mother. In some countries, such as Britain and the United States, the parents can donate these 'spare' blastocysts for medical research.

Adult stem cells are also called tissue-specific stem cells because each type of adult stem cell produces only a limited set of specialized cells characteristic of a particular tissue — epidermis, blood, and so on. In adults, tissue-specific stem cells are located throughout the body. The so-called hematopoietic stem cells in bone marrow and umbilical cord blood, which make all the different types of blood cells, are the easiest to isolate, and have been used in therapy for decades — as bone marrow transplants for diseases such as leukemia, where the normal development of blood cells has gone awry.

Other types of tissue-specific stem cells are usually found deep within tissues and are harder to get at and harder to study, especially in humans. Familiar examples are the epidermal stem cells which continually renew the outer layer of the skin as it gets worn away, and the epithelial stem cells in the gut, that are similarly continually replacing the gut lining. More recent discoveries are of bronchoalveolar stem cells from the lungs of adult humans, which are thought to renew the lining of parts of the lungs, for example. And adult stem cells have been found in the inner ear in mice that could be involved in renewing cells involved in balance sensing. But even when cells are discovered that appear to behave like stem cells when grown in the laboratory, it's hard to know whether they act like stem cells in the body, because their natural behavior is hard to observe.


Watch the video: Pregnancy 101. National Geographic (August 2022).