Schweizerischer Nationalfonds / Fonds national suisse
A model in a plastic dish now shows how the versatile placenta transports substances
Bern (ots)
There is little scientific evidence about how substances such as medications cross the placenta to the baby. A publication co-funded by the SNSF presents a realistic model to help understand this.
At least half of all women take medications during pregnancy, for example to treat a chronic condition or to manage complications. Many are concerned that medicinal products could have a negative impact on their unborn child. In fact, for most substances, little is known about whether and to what extent they are passed on to the baby. Due to a lack of data, as a precaution many medicines are therefore not licensed for pregnant women - although they may not pose any risk at all.
The placenta controls which substances - nutrients or medicines - are passed from the mother's bloodstream to the unborn baby. To do so, the substances must successfully cross two different cell layers. First, the densely packed trophoblast cells in the placenta, which are in contact with the mother's blood. Then, the slightly more permeable endothelial cells, which line the baby's blood vessels that extend deep inside the placenta.
Collected right after delivery
The problem is that up to now, there have not been any good models available with which to study the exchange of substances across this barrier. "Depending on the organism, the placenta works in very different ways. So, animal experiments do not always reflect what happens in humans," says biomedical scientist Christiane Albrecht, who is partly funded by the SNSF. Her team from the University of Bern has now developed a lab model that replicates transport processes in the human placenta better than previous methods.
To this end, the researchers placed the two cell layers into small plastic wells, with a permeable membrane separating them. The top layer consists of trophoblast cells, and the bottom layer of endothelial cells. If a substance is then added to the top layer, the researchers can observe whether and how much of it permeates the two cell layers and comes out the other side. This simulates the transport of substances from the mother via the placenta to the baby's bloodstream.
What is special about this system is that the cells come from the placenta and umbilical cord of very recent births. They therefore have capabilities that cell cultures grown in a lab lose during prolonged culture.
Certain substances are immediately expelled
"Our model effectively mimics the key functions in the placenta's microenvironment," says postdoctoral researcher Barbara Fuenzalida, the lead author of the study. The researchers were able to demonstrate, for example, that fat soluble substances such as caffeine diffuse through both cell layers - like they do in a pregnant woman's body.
They also showed that trophoblast cells contain the special transport proteins that direct nutrients such as amino acids and sugar to the baby in the womb. What is particularly important is that the lab model also contains the transporters that immediately expel the undesirable substances from the cell.
They include, for example, medicines such as the immunosuppressant cyclosporin or steroids. Cells cultured in the lab for a long time sometimes lost this ability. "Return transport is of course incredibly important to protect the unborn baby," says Albrecht.
A multi-purpose organ for 40 weeks
Another innovative aspect of the model is that the fluids that cover the cell layers are kept constantly moving using mini pumps. This mimics the maternal and foetal blood flow, which stimulates the key functions of the placenta. For example, the immersed trophoblasts in the model produced larger quantities of the pregnancy hormone chorionic gonadotropin than in a static fluid.
The researchers now want to use the new model not only to study drug pathways, but also the transport of other substances, such as iron and cholesterol. "The placenta is a fascinating organ that during the 40 weeks of pregnancy takes over various functions, including those of the lungs, gut, liver and hormone-producing organs," says Albrecht. "It's a pity that relatively little research is carried out on it."
If nothing else, such models can also help reduce the number of animal experiments performed - for example in drug development. However, the method is still too labour-intensive to be deployed on a large scale. Albrecht therefore says: "We next need to look at what we could further simplify to be able to use our system in a more routine way, for example for toxicology tests."
The text of this news and further information are available on the website of the Swiss National Science Foundation.
Contact:
Christiane Albrecht
University of Bern Institute of Biochemistry and Molecular Medicine
Bühlstrasse 28
3012 Bern
Phone: +41 31 684 41 08
Email: christiane.albrecht@unibe.ch