Lab-grown miniplacentas help better understand preeclampsia

A team scientist has developed “miniplacentas” in the laboratory and has used them to clarify how the placenta develops and interacts with the inner lining of the uterus, which could help better understand preeclampsia and, in the future, treat it.

The study, published this Wednesday in Cell Stem Cell, demonstrates that it is possible to experiment with a developing human placenta, instead of simply observing specimens, to study the main disorders of pregnancy.

The success of pregnancy depends on the development of the placenta in the first weeks of gestation. During this period, the placenta implants in the endometrium, the mucosal lining of the mother’s uterus, explains in a statement from the University of Cambridge.

The interactions between the cells of the endometrium and those of the placenta are decisive for its success. In particular, they are essential to increase maternal blood flow to the placenta, necessary for the growth and development of the fetus.

When these interactions do not work properly, they can lead to complications, such as preeclampsia, a disease that causes high blood pressure during pregnancy; This occurs in about six out of every 100 first pregnancies and can endanger the health of the mother and baby.

Although it affects millions of women a year around the world, it is still poorly understood. It usually occurs at the end of pregnancy, but to really understand it – predict and prevent it – you have to look at what happens in the first weeks, the university emphasizes.

Ashley Moffett, from the Department of Pathology at Cambridge, reminds us that most major disorders, such as pre-eclampsia, stillbirth or growth retardation, depend on failures in the way the placenta develops in the first weeks.

It is, he adds, an incredibly difficult process to study: the period after implantation, when the placenta becomes embedded in the endometrium, is often described as a “black box of human development”.

Moffett and researchers from the Friedrich Miescher Institute (Switzerland) and the Wellcome Sanger Institute used “miniplacentas”, a cellular model of the early stages of the placenta, to gain insight into early pregnancy and improve understanding of reproductive disorders.

Known as “trophoblast organoids”are grown from placental cells (organoids are millimetric 3D versions of human organs that are manufactured, using cell culture methods, in the laboratory).

In previous work, the team identified genes that increase the risk of or protect against diseases such as preeclampsia.

These studies highlighted the important role of immune cells unique to the uterus, known as “uterine natural killer cells”; These are grouped in the lining of the uterus, where the placenta is implanted.

In their new study, the team applied proteins secreted by those killer cells to the organoids so they could mimic the conditions under which the placenta implants.

The scientists identified specific proteins that were crucial in helping the organoids develop. These contribute to the success of implantation, allowing the placenta to invade the uterus and transform the mother’s arteries.

“If the cells are not able to invade correctly, the arteries of the uterus do not open and the placenta, and therefore the baby, do not receive nutrients or oxygen, which is why problems arise later,” the researcher points out.

The description of this technique was already published in 2018, also in Nature; Now scientists have released new data, identified other proteins and tested some.