Summer Blog Series with the 3RCC, part 4: Closer to solving the Preeclampsia Puzzle: In Vitro Trophoblast Cells in Action!

Preeclampsia is a serious pregnancy complication affecting 5-8% of all pregnancies and is among the leading causes of maternal and fetal mortality worldwide. Despite its prevalence, the exact cause of preeclampsia remains unclear, making it difficult to develop effective treatments. A comprehensive understanding and accurate modelling of this condition are essential steps toward enhancing maternal and fetal health outcomes.

In the past, animal models that mimic preeclampsia have aided scientists in understanding this condition. However, a team from the University of Bern, which received funding from the 3RCC in 2019 and is led by Prof. Christiane Albrecht, successfully uses specific cells from the human placenta, called trophoblasts, to study preeclampsia in vitro¹, avoiding the need for animal models. Preeclampsia is often associated with hypoxia—low oxygen supply to the placenta—which, for example, can hinder proper blood vessel formation. By mimicking hypoxia in the lab, the researchers replicated key features seen in preeclampsia, including markers of angiogenesis², oxidative stress³, and inflammation. Their study, published in Cells, suggests this new cell model can help us better understand this condition.

The team is developing an advanced in vitro co-culture model (a model used to study how different cells interact with each other or with their environment) using trophoblast and other cells to recreate the placenta-blood barrier, mimicking the placenta’s structure and how it works.  This model uses a microfluidic system, which simulates how things flow in the body, and ‘would be highly relevant for testing medications administered during pregnancy and verifying their ability of materno-fetal transfer,’ says Dr. Albrecht. Currently, when doctors decide whether a medicine is safe during pregnancy, they often don’t know for sure. Prof. Albrecht’s work could change that by providing a safe way to test medicines before they’re used in pregnant patients. Moreover, the team is working to reduce the use of animal-derived products in their culture system⁴, with ongoing collaborations with the pharma industry.  

Aligned with the 3Rs Principle⁵, the model developed by Christiane Albrecht’s lab not only offers significant advantages in replacing and reducing the use of animals and animal-derived products in this line of research but holds great potential to advance our understanding of preeclampsia and thus may lead to better therapeutic strategies to combat this life-threatening condition.

¹ “In vitro” is a Latin term that translates to “in glass.” In scientific contexts, it refers to experiments or processes conducted outside of a living organism, typically in a controlled laboratory environment. In vitro experiments often involve isolated cells, tissues, or organs, allowing researchers to study biological phenomena under controlled conditions. This approach is commonly used in fields such as cell biology, microbiology, pharmacology, and toxicology to investigate cellular processes, drug effects, disease mechanisms, and more.

² Angiogenesis: the formation of new blood vessels

³ Oxidative stress: Occurs when there are too many harmful molecules called free radicals in the body, which can damage cells.

⁴ A culture system is a controlled environment designed to support the growth and development of cells, tissues, or microorganisms outside their natural context, typically within a laboratory setting.

⁵ 3Rs Principle: The principles of the 3Rs (Replacement, Reduction and Refinement) concerning animal experimentation were postulated in 1959 by William Russell and Rex Burch in a book entitled Principles of Humane Experimental Technique. The principles are today internationally widely recognized by scientists as a moral obligation. They are moreover implemented in many national legislations on animal protection.

Authors: Christopher Cederroth, Jessica Lampe & Robbie I’Anson Price, Swiss 3R Competence Centre.

Reference: Fuenzalida B, Kallol S, Zaugg J, Mueller M, Mistry HD, Gutierrez J, Leiva A, Albrecht C. (2022). Primary Human Trophoblasts Mimic the Preeclampsia Phenotype after Acute Hypoxia–Reoxygenation Insult.Cells. 11:1898. https://doi.org/10.3390/cells11121898