Placental Stem Cell Provides Model System for Pregnancy Complications

Preeclampsia occurs during pregnancy, and is characterized by a gradual rise in blood pressure to dangerous levels. It usually presents after the 20th week of pregnancy, and can even persist after delivery.

How common is preeclampsia? In the United States, preeclampsia affects 5-8% of all births. Among the women of Canada, the United States, and Western Europe, the births affected by preeclampsia range from 2-5%. (5,6) In the developing world, the percentage of births affected by preeclampsia range from 4% of all deliveries to as high as 18% in parts of Africa. In Latin America, preeclampsia is the number one cause of maternal death.

Globally, ten million women develop preeclampsia each year, and 76,000 pregnant women die each year from preeclampsia and related disorders. The number of babies who die from these disorders is thought to be on the order of 500,000 per year.

In developing countries, a woman is seven times more likely to develop preeclampsia than a woman in a developed country, and between 10-25% of those cases will result in the death of the mother.

Now that I’ve hopefully convinced you that preeclampsia is a problem, how do we address it? Research in laboratory mice have told us a great deal about preeclampsia and other disorders that arise during pregnancy, but finding a sound model system that can be used to develop effective and safe treatments requires something closer to humans.

To that end, Hanna Mikkola and her research team and the University of California, Los Angeles Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research (that’s a mouthful), have identified a type of progenitor cell that is key to the growth of a health placenta.

Work in laboratory mice has shown that preeclamsia often arises because of a malformed placenta. This poorly-formed placenta does not provide enough oxygen and nutrients for the growth needs of the baby at the fetal stages of development, and the mother’s body responds by increasing the mother’s blood pressure in order to increase blood flow through the placenta.

The work by Mikkola and her colleagues have provided physicians and developmental biologists with a new “tool box” for understanding the development of the placenta and the different cell types that compose it. Hopefully, various complications during pregnancy might be due to malfunctions of these particular cell types and the progenitor cells that produce them.

Mikkola and others started with laboratory mice, since it is possible to label single cells in mouse embryos and track exactly where those cells and their progeny go and what they do. The powerful genetic tools available in laboratory mice also allows scientists to identify the various biochemical signaling pathways that cells use to communicate with other cells during placental development. Also, if something goes wrong with particular cell signaling pathways, the mouse model allows scientists to precisely characterize the developmental consequences of much dysfunction.

Through their work in the mouse, Mikkola and her co-workers identified a placental progenitor cells called the Epcamhi labyrinth trophoblast progenitor or LaTP. The LaTP is like a multipotent adult of tissue-specific stem cell that can become many of the cells required to make the placenta.

Mikkola and her group also showed that the “c-Met” signaling pathway was required to sustain the growth of LaTPs during placental development and that this same signaling pathway was required to form a specific group of cells (syncytiotrophoblasts) that form the interface between the placenta and the mother’s endometrium. Elimination of c-Met signaling completely compromised the growth of the fetus and its development.

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This new cell type should provide a wealth of opportunities to examine complications during pregnancy like preeclampsia and others and design treatments that can save the lives of mothers and their babies.

Cloned embryos can’t fool a womb

See the following link for an interesting paper on the ability of the womb to discern between a cloned embryo and an embryo made by means of fertilization. See this link for the article.

Embryonic stem cells from cloned embryos are indistinguishable from those made from embryos made by fertilization.  They express the same genes (see  DJ Guo et al., Proteomics. 2009 Apr 22, and this article), show the same biological behaviors (see this link for this paper), show normal embryonic stem cell morphology, express key stem-cell markers, and can differentiate into multiple cell types in vitro and in vivo (JA Byrne, Nature 450 (2007): 497-502).

Since embryonic stem cells are made from the internal cells of the embryo (the inner cell mass), the inner cell mass cells from cloned embryos are rather normal (ML Condic, Cell Proliferation 41, suppl 1: 7-19).  However, the outer layer of cells (trophectoderm) that engage the endometrium and work with it to implant the embryo into the inner layer of the uterus do not differentiate normally in cloned embryos (DR Arnold et al. Reproduction 132, no. 2 (2006): 279­-90).  Trophoblast cells  in cloned embryos are normal at the early stages (S. Kishigami et al., FEBS Letters 580, no. 7 (2006): 1801-6), but they go on to make abnormal placentas (DR Arnold et al, Placenta 29 Suppl A (2007): S108-10).

Now this paper shows that the differentiating placenta of the cloned embryo does not interact normally with the surrogate mother’s uterus.  This is probably one of the main reasons why cloned embryos and fetuses tend to die prior to birth.  The endometrial cells of the mothers who were carried the cloned embryos showed substantial variation in the genes they expressed in comparison to endometria that carried in vitro fertilized embryos (S. Bauersachs et al., PNAS 106, no. 14 (2009): 5681-6).  Thus cloned embryos fail to properly communicate with the mother’s uterus.

Implantation is a very complex process.  It requires cross talk between the embryo and the uterus.  Without this cross talk, implantation does not occur successfully.  Without successful implantation, the embryo perishes.

Here again we find another reason to not clone humans.  We are subjecting them to a process that is less robust than fertilization.  The chances of the embryo surviving are far less than an embryo concieved in the usual manner (fertilization).  We should simply ban this process in humans overall.