The placental system: a realistic model can help treat abnormalities in pregnant women

Russian scientists have created a more advanced cell model of the placenta, which better matches the natural structure of the organ than existing analogs. Medics achieved this by placing between the traditional cell layers of such systems a layer of macrophages, which play an important role during pregnancy and are responsible for ensuring that the fetus is not rejected by the mother's body. The development is intended to find new methods of treating complications and creating drugs. Clinical trials involving real patients pose a serious problem because they contradict medical ethics, experts said. The invention can noticeably simplify and speed up this process, they believe.

Placenta model

Specialists of the Peoples' Friendship University of Russia named after Patrice Lumumba together with colleagues from the V.I. Kulakov National Research Center of Obstetrics, Gynecology and Perinatology, the National Research University Higher School of Economics and Skoltech have developed a realistic model of the "placenta on a chip", which more accurately reflects the features of the organ than existing analogs. Between the traditional for such developments layers of syncytiotrophoblast (performs the function of absorption of nutrients from the mother's blood) and endothelium scientists have placed a layer of collagen gel with macrophages, which is more consistent with the structure of the natural placenta.

- Macrophages are also part of the placenta, a very important part that, according to our data, even determines some pathologies. But macrophages are not present in the current models. In reality, the placental villus has several layers - it is the syncytiotrophoblast that covers it, and inside it are endothelial cells. In the middle between them is the stroma, and in it are macrophages. Before us, no one has ever discussed and used this cellular component, although it is necessary," said Polina Vishnyakova, associate professor of the Department of Histology, Cytology and Embryology at the PFUR Medical Institute.

Photo: TASS/Business Online/Sergei Yelagin

As the researcher explained, the placenta is a temporary organ. When a fertilized cell begins to divide, two components are formed: embryoblast, from which the embryo itself develops, and around - trophoblast, from which the placenta develops and embeds in the uterus. Its function is to nourish and exchange nutrients. The fetus can not breathe on its own, so the transportation of oxygen occurs just in the placenta. It is washed by the mother's blood and through the transplacental barrier there is an exchange of oxygen and carbon dioxide with the fetus.

At the same time, macrophages are localized everywhere in the body. These are cells of innate immunity, which are present in any organ. They are responsible for phagocytosis - absorption of pathogenic substances and bacteria. Macrophages eat dead, virus-infected and can eat tumor cells. In the placenta, they have the most important function - to maintain a normal immune tolerance, so that the baby is not rejected by the mother's body.

What the development is used for

- Our development can be used to model and find ways to treat major obstetric syndromes, such as pre-eclampsia. This is a very serious condition that affects up to 7% of all pregnancies. It manifests as high blood pressure and protein in the mother's urine after the 20th week of pregnancy. The patient can actually die if she is not delivered, such as by cesarean section. When the placenta is removed, the woman immediately feels better and all symptoms go away," said Polina Vishnyakova.

According to the specialist, pregnant women are a special group of patients, on which it is very difficult to conduct clinical trials of drugs. Therefore, mice are often used for this purpose, but their physiology is very different from that of humans. With the help of the model proposed by scientists, it is possible to calculate the total transplacental transport of substances, that is, how much of the drug gets from the blood of the mother into the blood of the child through the placenta. For example, now the researchers are conducting experiments to find out in what concentrations there penetrates nicotine.

Photo: Izvestia/Mitriy Korotayev

As noted by the head of the embryology laboratory of the reproduction center "Life Line", embryologist Tatiana Troshina, on such models can be studied, how the development of a person in the early stages and test new drugs. The placenta is a complex structure consisting of cells of maternal and embryonic origin, violation of the formation and functions of the placenta can lead to delayed intrauterine development and death of the embryo, so the development of technology "placenta on a chip" seems extremely important.

- Indeed, macrophages play an important role in the whole organism, including the placenta. It has long been known that they eat some cells, but about 10 years ago another type of macrophages was discovered, which are active at the time of tissue repair from inflammation. Most likely, they control that the fetus is not rejected by the mother's body. Now they are discovering more and more of their functions, including during pregnancy, - said senior researcher at the Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences Mikhail Bolkov.

Photo: Izvestia/Eduard Kornienko

The solution proposed by the scientists is very progressive in terms of the development of science, and biomedicine in particular, said Daria Kazakova, an obstetrician-gynecologist at the SM-Clinica Center for Reproductive Health. All over the world there is a huge problem with conducting the clinical stage of trials on pregnant women, as it is almost always contrary to medical ethics and is simply impossible.

- Nevertheless, at the moment it is doubtful that we can completely replace the clinical trial phase using the proposed technology. Modeling the situation in the laboratory, even using the most modern technologies, is not equal to the same processes in a living organism. And that is why the clinical stage of trials is always conducted on humans, and the group of subjects must be selected in a special way, and a huge number of factors are taken into account. But as for the preclinical phase of trials, I think this is really progress that will soon enter our lives," she said.

Photo: RIA Novosti/Vladimir Astapkovich

"In the preclinical phase, you can compare the data from the lab animal trials with the data from the placenta-on-a-chip. And if at this comparison statistically significant differences are not obtained, it is possible to really cheapen, reduce in time and make more humane this stage, summarized the expert.